MHC — Q-Bank
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Unit 10 Question Bank

MHC · genes, structure, distribution, polymorphism and peptide binding
16 MCQ6 Definitions7 Fill-in6 True/False3 Brief
The five tabs are the five sections of the real paper. Items tagged Past Paper 2019 or 2020 are the genuine questions, reproduced verbatim. Items tagged Slide come from the TMU lecture; items tagged Janeway's are built from the textbook to cover examinable ground. Nothing is invented. Janeway's 10e is a reflowed edition with no printed page numbers, so it is cited by numbered section (§1-14), not by page.
0 / 29 answered
1The antigen-binding cleft of MHC class II molecules locates between:
A. α1 and β1
B. α1 and α2
C. α1 and β2
D. α1 and β2-microglobulin
Answer: A
α1 and β1. Class II is a two-chain molecule, so its groove is built from one domain of each chain. Class I has only one MHC-encoded chain and must therefore build its groove from two domains of the same chain — α1 + α2. β2 is where CD4 binds; β2-microglobulin is class I's non-MHC support protein.Past Papers 2019 & 2020, Section III Q6 · confirmed by TMU Lecture 10 — MHC Slide 32
2All the following cells express HLA class I molecules except:
A. T cells
B. Mature erythrocytes
C. B cells
D. Macrophages
Answer: B
Class I is expressed on all nucleated cells — and a mature red cell has extruded its nucleus. This is also why transfusion is matched on ABO and Rh rather than HLA: the transfused cells carry no class I to match.Past Papers 2019 & 2020, Section III Q7 — verbatim, both years
3MHC class II molecules are normally expressed on:
A. All nucleated cells
B. All cells including erythrocytes
C. Dendritic cells, macrophages, B cells and thymic stromal cells
D. T lymphocytes only
Answer: C
Class II is confined to the professional APCs plus thymic stroma. 'All nucleated cells' describes class I — and that swap is exactly True/False Q12. The restriction is deliberate: engaging a CD4⁺ helper cell starts an immune response, and that authority belongs only to cells whose job is sampling the environment.TMU Lecture 10 — MHC Slide 15
4On which chromosome is the human MHC (HLA complex) located?
A. Chromosome 17
B. Chromosome 2
C. Chromosome 22
D. Chromosome 6
Answer: D
Chromosome 6 in humans. Chromosome 17 is where the mouse H-2 complex sits — a distractor drawn from the same lecture slide.TMU Lecture 10 — MHC Slide 5
5Which genes belong to the HLA class II region?
A. HLA-DP, HLA-DQ and HLA-DR
B. HLA-A, HLA-B and HLA-C
C. C4, C2 and Bf
D. HLA-E and HLA-G
Answer: A
DP, DQ, DR are class II and encode both α and β chains. A, B, C are class I and encode only the α chain. C4, C2, Bf are class III — complement components. HLA-E and HLA-G are non-classical class I genes.TMU Lecture 10 — MHC Slide 7
6Which molecules are encoded in the MHC class III region?
A. The α chains of class I molecules
B. Complement C4, C2 and factor B, plus TNF and HSP70
C. The α and β chains of class II molecules
D. β2-microglobulin
Answer: B
Class III has nothing to do with peptide display — it encodes complement components from Unit 4, plus TNF and heat-shock protein 70. A single genetic region therefore carries both the display system and several of the effectors that act on what it reveals. β2-microglobulin is notably not MHC-encoded at all.TMU Lecture 10 — MHC Slides 7, 9
7MHC class I molecules consist of:
A. One α chain and one β chain, both MHC-encoded
B. Two identical α chains
C. One MHC-encoded α chain plus β2-microglobulin
D. An α chain plus a J chain
Answer: C
β2-microglobulin is not encoded within the MHC and does not form part of the groove — it is a structural support. That is precisely why class I must build its cleft from α1 + α2, two domains of its single MHC chain.TMU Lecture 10 — MHC Slides 11, 26
8CD8 binds to which domain of MHC class I?
A. α1
B. α2
C. β2-microglobulin
D. α3
Answer: D
α3 — a non-polymorphic region away from the peptide groove, so the grip is independent of which peptide is displayed. CD4 correspondingly binds the β2 domain of class II. α1 and α2 form the class I groove.TMU Lecture 10 — MHC Slide 26
9Which statement correctly contrasts the peptide-binding clefts?
A. Class I has a closed cleft binding 8–10 aa; class II has an open cleft binding 13–18 aa
B. Class I has an open cleft binding 13–18 aa; class II a closed cleft binding 8–10 aa
C. Both clefts are closed and bind 8–10 aa
D. Both clefts are open and peptide length is unconstrained
Answer: A
The closed/open distinction explains the length rule. A closed cleft is sealed at both ends, so the peptide must fit exactly — hence the tight 8–10 residue range and anchors gripping both termini. An open cleft lets the peptide overhang, so length is not constrained.TMU Lecture 10 — MHC Slides 32–33
10Anchor residues of peptides bound by MHC class I are located:
A. Distributed along the length of the peptide
B. At both ends of the peptide
C. Only at the N-terminus
D. In the transmembrane region
Answer: B
Class I anchors sit at both ends because the closed cleft grips both termini. Class II anchors are distributed along the length, since the open cleft holds the peptide along its middle and lets the ends hang out.TMU Lecture 10 — MHC Slides 29, 31, 33
11Co-dominance of MHC genes means that:
A. Only the allele from one parent is expressed per cell
B. MHC genes are expressed only after antigen exposure
C. Both maternal and paternal gene products are expressed in the same cell
D. Class I and class II are expressed together on every cell
Answer: C
There is no allelic exclusion in MHC expression — unlike antigen receptors, where each lymphocyte uses one allele. Co-dominance doubles the number of different MHC molecules an individual carries, widening the range of peptides that can be presented.TMU Lecture 10 — MHC Slide 18
12An MHC haplotype is:
A. The complete set of MHC alleles from both parents
B. The number of alleles at a given MHC locus
C. The peptide-binding motif of one MHC molecule
D. The particular combination of MHC alleles found on a single chromosome
Answer: D
A haplotype is one chromosome's worth of MHC alleles, and it is transmitted as a single unit in most cases — which is why HLA matching between siblings follows simple inheritance patterns and why a full sibling has a one-in-four chance of being a complete match.TMU Lecture 10 — MHC Slide 20
13Linkage disequilibrium refers to:
A. The difference between the observed frequency of an allele combination and that expected from individual allele frequencies
B. Failure of MHC genes to segregate at meiosis
C. Loss of MHC expression on tumour cells
D. Unequal expression of maternal and paternal alleles
Answer: A
Certain allele combinations occur together far more often than chance would predict — the haplotype behaves as a unit rather than reassorting freely. Loss of MHC expression on tumour cells is a different phenomenon entirely, and it is what makes those cells vulnerable to NK missing-self killing (Unit 9).TMU Lecture 10 — MHC Slide 21
14Which is NOT one of the stated properties of MHC?
A. Polygeny
B. Allelic exclusion
C. Polymorphism
D. Co-dominance
Answer: B
MHC shows no allelic exclusion — that is the whole point of co-dominance. Allelic exclusion belongs to antigen receptors, where each lymphocyte expresses only one allele so that it has a single specificity. The five MHC properties are polygeny, polymorphism, co-dominance, haplotype and linkage disequilibrium.TMU Lecture 10 — MHC Slides 18, 22
15Which is a function of MHC molecules?
A. Binding antigen directly without processing
B. Activating complement by the classical pathway
C. Directing T-cell differentiation in the thymus
D. Serving as the receptor for HIV
Answer: C
MHC has three stated functions: presenting peptide to T cells, imposing MHC restriction, and directing T-cell differentiation in the thymus through positive and negative selection. Note that MHC does not merely impose restriction — positive selection creates it. Complement activation is antibody's job; the HIV receptor is CD4.TMU Lecture 10 — MHC Slide 34
16A tumour cell that has lost MHC class I expression escapes CD8⁺ CTLs but becomes vulnerable to:
A. CD4⁺ helper T cells
B. Complement fixation by IgM
C. γδ T cells via MHC restriction
D. NK cells, through missing-self recognition
Answer: D
Losing class I removes the ligand for NK inhibitory receptors, so activation predominates and the NK cell kills — the loophole-closing design from Unit 9. The two killers are complementary: the CTL kills cells showing the wrong thing, the NK cell kills cells showing nothing.TMU Lecture 10 — MHC Slide 15 · Unit 9 · Janeway's Immunobiology 10e
1 MHC (major histocompatibility complex) — 3 marks+
A cluster of genes encoding membrane glycoproteins that display peptide antigen to T cells. In humans it is the HLA complex on chromosome 6; in mice, H-2 on chromosome 17. Class I genes (HLA-A, B, C) encode the α chain of class I molecules; class II genes (HLA-DP, DQ, DR) encode the α and β chains of class II molecules; class III encodes complement C4, C2 and Bf, plus TNF and HSP70.Past Paper 2020, Section I Q4 · TMU Lecture 10 — MHC Slides 3, 5, 7
2 MHC class I molecule — 3 marks+
A molecule composed of one MHC-encoded α chain (domains α1, α2, α3) together with β2-microglobulin, which is not MHC-encoded. Its peptide-binding cleft is formed by α1 and α2, is closed, and binds peptides of 8–10 amino acids anchored at both ends. CD8 binds the α3 domain. Expressed on all nucleated cells.TMU Lecture 10 — MHC Slides 11, 15, 26, 32
3 MHC class II molecule — 3 marks+
A molecule composed of an α chain and a β chain, both MHC-encoded. Its peptide-binding cleft is formed by α1 and β1, is open, and binds peptides of 13–18 amino acids with anchor residues distributed along their length. CD4 binds the β2 domain. Expressed only on dendritic cells, macrophages, B cells and thymic stromal cells.TMU Lecture 10 — MHC Slides 12, 15, 26, 32
4 Polymorphism of MHC — 3 marks+
The presence of multiple alleles at a genetic locus within the species — HLA-A has 303 alleles, HLA-B 559, HLA-C 150, HLA-DRB 440. Unlike antibody diversity, which is generated within each individual, MHC variation lies between individuals, so it protects the species rather than the person: no pathogen can evade every human's MHC at once.TMU Lecture 10 — MHC Slide 16
5 Haplotype and linkage disequilibrium — 3 marks+
A haplotype is the particular combination of MHC alleles found on a single chromosome, transmitted as a single unit in most cases. Linkage disequilibrium is the difference between the frequency observed for a particular combination of alleles and that expected from the frequencies of the individual alleles.TMU Lecture 10 — MHC Slides 20–21
6 Anchor residues — 3 marks+
Structurally related residues by which a peptide binds into the MHC groove. Anchor residues differ between different alleles of MHC but are similar for all peptides that bind the same MHC molecule — so each allele has a characteristic binding motif, and a single MHC molecule can present thousands of different peptides sharing that motif.TMU Lecture 10 — MHC Slide 29
1In humans the MHC is called the  ?  complex and is located on chromosome  ? ; in mice it is called  ?  and lies on chromosome  ? .4 mark(s)
Phrasing confirmed against the student review sheet and the lecture.
TMU Lecture 10 — MHC Slides 5, 8
2The genes coding for class I MHC molecules are  ? ,  ?  and  ? ; the class II genes are  ? ,  ?  and  ? .6 mark(s)
Class I genes encode only the α chain; class II genes encode both α and β chains.
TMU Lecture 10 — MHC Slide 7
3The peptide-binding cleft of MHC class I is formed by  ?  and  ? ; that of class II by  ?  and  ? .4 mark(s)
This is MCQ Q6. Count the MHC-encoded chains: class I has one, so both groove walls come from it; class II has two, so it takes one domain from each.
Past Papers 2019 & 2020, Section III Q6 · TMU Lecture 10 — MHC Slide 32
4MHC class I is expressed on  ?  cells, whereas class II is expressed only on  ? ,  ? ,  ?  and thymic stromal cells.4 mark(s)
Class I reports (any cell can be infected); class II recruits (only professional APCs may start a response). True/False Q12 swaps the two rules.
TMU Lecture 10 — MHC Slide 15
5CD8 binds the  ?  domain of MHC class I; CD4 binds the  ?  domain of MHC class II.2 mark(s)
Both are non-polymorphic regions away from the groove, so the co-receptor grip does not depend on which peptide is displayed.
TMU Lecture 10 — MHC Slide 26
6MHC class I binds peptides of  ?  amino acids in a  ?  cleft; class II binds peptides of  ?  amino acids in an  ?  cleft.4 mark(s)
The cleft shape dictates the length rule — a closed cleft grips both termini, an open one lets the peptide overhang.
TMU Lecture 10 — MHC Slide 32
7The five properties of MHC are  ? ,  ? ,  ? ,  ?  and  ? .5 mark(s)
Note what is absent: allelic exclusion. Both parental alleles are expressed in every cell.
TMU Lecture 10 — MHC Slide 22
1HLA class II molecules can be expressed on the surface of all nucleated cells.
FALSE
FALSE. That describes class I. Class II is restricted to dendritic cells, macrophages and B cells plus thymic stroma. The statement is true of the wrong class — the neatest kind of trap, and it appears unchanged in both papers.Past Papers 2019 & 2020, Section IV Q12 — verbatim, both years
2β2-microglobulin is encoded within the MHC.
FALSE
False. β2-microglobulin associates with the class I α chain but is not MHC-encoded and forms no part of the peptide groove — which is exactly why class I must build its cleft from α1 + α2 of its single MHC chain.TMU Lecture 10 — MHC Slides 11, 26
3MHC genes show allelic exclusion, so each cell expresses only one parent's alleles.
FALSE
False — MHC is co-dominant with no allelic exclusion; both maternal and paternal products appear in the same cell. Allelic exclusion belongs to antigen receptors, where one lymphocyte must have one specificity.TMU Lecture 10 — MHC Slide 18
4Mature erythrocytes express HLA class I molecules.
FALSE
False. Class I is on all nucleated cells, and mature red cells have no nucleus — this is MCQ Q7. It is also why transfusion compatibility runs on ABO and Rh rather than HLA.Past Papers 2019 & 2020, Section III Q7
5A single MHC molecule can bind many thousands of different peptides.
TRUE
True. Each MHC allele requires only a couple of specific anchor residues at fixed positions; everything between them is unconstrained. MHC is deliberately low-specificity and high-breadth — the specificity is supplied afterwards by the TCR reading the peptide–MHC combination.TMU Lecture 10 — MHC Slide 29
6The MHC class III region encodes complement components.
TRUE
True — C4, C2 and factor B, together with TNF and HSP70. A single genetic region therefore carries both the peptide-display system and several of the effector molecules that act on what it reveals.TMU Lecture 10 — MHC Slides 7, 9
1 Compare MHC class I and class II molecules. 6 marks
Class IClass II
GenesHLA-A, B, CHLA-DP, DQ, DR
ChainsOne MHC-encoded α chain + β2-microglobulin (not MHC-encoded)α chain and β chain, both MHC-encoded
Peptide-binding cleftα1 + α2α1 + β1
Nature of cleftClosedOpen
Peptide size8–10 aa13–18 aa
Anchor residuesAt both endsDistributed along the length
Co-receptorCD8, at α3CD4, at β2
Expressed onAll nucleated cellsDC, macrophages, B cells, thymic stroma
Presents toCD8⁺ CTLCD4⁺ helper T cell

Memory aid: class I × CD8 = 8 and class II × CD4 = 8.

Marking guide: 0.75 per row. The cleft composition and the distribution rows are the two that the paper actually tests, and neither can be omitted.
2 Describe the properties of MHC. 6 marks

① Polygeny — several different MHC genes exist (A, B, C; DP, DQ, DR), so each person expresses several different class I and class II molecules.

② Polymorphism — multiple alleles at each locus within the species: HLA-A 303 alleles, HLA-B 559, HLA-C 150, HLA-DRB 440.

③ Co-dominance — both maternal and paternal gene products are expressed in the same cell; there is no allelic exclusion.

④ Haplotype — the particular combination of MHC alleles on a single chromosome, transmitted as a single unit in most cases.

⑤ Linkage disequilibrium — the difference between the observed frequency of an allele combination and that expected from the individual allele frequencies.

Significance: polymorphism lies between individuals rather than within one, so it defends the species — no pathogen can evade every person's MHC. Co-dominance and polygeny widen the peptide repertoire of each individual.

Marking guide: 1 mark per property with a correct definition, plus 1 for the significance.
3 What are the functions of MHC molecules? 6 marks

① Antigen presentation. MHC molecules bind peptides derived from pathogens and display them to T cells. Class I presents endogenous (cytosolic) peptide to CD8⁺ CTLs; class II presents exogenous (vesicular) peptide to CD4⁺ helper T cells. Because a T-cell receptor recognises antigen only as peptide bound to MHC, this is the sole route by which T cells see antigen at all.

② MHC restriction. The interaction between antigen-presenting cell and T cell is MHC-restricted — a given T cell recognises peptide only in the context of a particular MHC molecule.

③ T-cell differentiation in the thymus. MHC molecules on thymic epithelial cells drive positive selection (conferring self-MHC restriction and committing the cell to CD4 or CD8) and, on thymic DCs and macrophages, negative selection (conferring self-tolerance). MHC therefore does not merely impose restriction — it creates it.

Also: MHC class I is the ligand for NK inhibitory receptors, so its loss triggers missing-self killing; and MHC differences between individuals are the basis of graft rejection.

Marking guide: 2 marks per function. Linking function 3 to positive and negative selection specifically is the discriminating detail.