CD Molecules and Adhesion Molecules

By the late 1970s laboratories around the world were raising monoclonal antibodies against lymphocyte surfaces — the hybridoma technique from Unit 3 had made it easy. The trouble was that each lab named its own antibody, and nobody could tell whether two antibodies from two cities were binding the same molecule or different ones. The literature was becoming unusable.

The fix was administrative rather than scientific, and it worked. Antibodies were pooled and compared, and those that recognised the same surface molecule were grouped into a cluster, which was given a number. That is all a CD number is: a shared address for a surface molecule, agreed so that everyone means the same thing. It is why you will spend the next several units learning numbers rather than names — the numbers came first, and the function was often worked out afterwards.

That second sentence is the examinable one and it is easy to skim past. The name is not arbitrary — it records the observation that surface markers change as a cell grows up. A given CD molecule may be present on an immature cell and gone from the mature one, or the reverse. This is precisely why CD markers are useful clinically: they let you read a cell's identity and its developmental stage off its surface.

You are not expected to learn 247 numbers. What you need is the handful that identify the major cell types and the handful that do a job you will meet again. Read the table by column first — which cell owns which markers — then by row for the function.

Three of these are worth marking now, because they are the answer to real exam questions you meet in later units. CD40 on the B cell receives the crucial second signal from the T cell's CD40L (Units 7 and 8). CD28 on the T cell receives its second signal from B7 (Unit 7). And CD21 is part of the B-cell co-receptor complex with CD19 and CD81 — the subject of a True/False question whose wrong answer is CD20 (Unit 8).

Cytokines, in Unit 5, were how immune cells shout across a gap. Adhesion molecules are how they hold on. And holding on turns out to matter more than it sounds: an immune cell that cannot stick cannot leave a blood vessel, cannot form a stable contact with an antigen-presenting cell, and cannot reach the tissue where it is needed.

There are four protein families, and the exam wants them named: selectins, mucin-like molecules, the immunoglobulin superfamily, and integrins. That order is worth keeping, because — as §7 will show — it is very nearly the order in which they are used.

The deck gives three functions, and they map cleanly onto three later units — which is the best reason to learn them now rather than meeting them cold.

• Co-receptors and co-stimulators in the immune response. Some CAMs act as co-receptors — CD4 and CD8 — and some as co-stimulators — CD28, CD80 and CD86 (B7). This is the two-signal requirement for T-cell activation, which is Unit 7.
• Leukocyte migration and inflammation. Getting cells out of the blood and into inflamed tissue — §7 below.
• Lymphocyte homing. The CAMs responsible are called lymphocyte homing receptors (LHR) on the lymphocyte and addressins on the tissue — §8 below.

Notice that function 1 quietly answers a question students often ask: why are CD4 and CD8 adhesion molecules when their job is to identify helper and cytotoxic T cells? Because their job is adhesion — they grip the MHC molecule on the antigen-presenting cell and hold the contact together while the TCR reads the peptide. The lineage marker and the adhesion function are the same thing seen from two angles.

Here is where the four families are used in sequence. Janeway's calls it the recruitment of circulating leukocytes to inflamed tissue, and it happens in four steps, each using a different adhesion family in turn.

The endothelium is not a passive wall in this. Macrophage-derived cytokines, especially TNF-α, activate it — triggering release of preformed P-selectin from storage granules (Weibel–Palade bodies) onto the surface within minutes. That is the link back to Unit 5: the cytokine does not do the sticking, it licenses the sticking.

The same machinery, used for a different purpose. Migration into inflamed tissue is an emergency response; homing is the routine traffic that keeps lymphocytes circulating through the right compartments. The molecules have their own names: the receptor on the lymphocyte is a lymphocyte homing receptor (LHR), and the tissue-specific ligand it recognises is an addressin.

The word addressin is well chosen — the tissue is displaying its address, and the lymphocyte is carrying a receptor that reads only certain addresses. Which addresses a lymphocyte can read depends on what it is and what it has done.

Why this small unit matters later

No past-paper item has yet been set from this deck alone. Its value is that it supplies the vocabulary for four questions that are set, in later units — so time spent here is repaid three units from now.

The whole unit on one screen