The MHC (major histocompatibility) complex is a collection of genes on chromosome 6. It’s organized into three regions: the class I region, the class II region, and the class III region. Class I genes encode glycoproteins expressed on the surface of nearly every nucleated cell in the body. These glycoproteins, called MHC I receptors, present antigens (proteins made within that particular cell) to CD8+ T cells. Class II genes encode glycoproteins expressed only on the surface of antigen-presenting cells (macrophages and dendritic cells). These glycoproteins, called MHC II receptors, present antigens (which that antigen-presenting cell has eaten and processed) to CD4+ T cells. The MHC III region encodes a bunch of things, including complement proteins and cytokines.

So what?

Well, your T cells can’t recognize antigen unless it’s shown to them by an MHC receptor (the books say “presented in the context of an MHC receptor” but I like simpler words better). Helper (CD4 +) T cells recognize antigens only when they are presented by MHC II receptors; cytotoxic (CD8 +) T cells recongize antigens only when they are presented by MHC I receptors.

How are you supposed to remember which cells have MHC I receptors and which have MHC II receptors, and which T cell subset recognizes each one? I think of it like this. The MHC I receptor is kind of a low-class, ordinary, run-of-the-mill receptor (hence the common-sounding “I” designation). It’s present on virtually all nucleated cells in the body. The MHC II receptor is a high-class, specialized, advanced kind of receptor (hence the higher “II” designation). Only certain kinds of cells (antigen presenting cells) get to have this receptor. I’m sure that’s not why they named them that – but it helps me remember the numbers if I think of them in this way.

As to the cells that recognize each type of receptor – if you can remember the above, then you can figure out which type of T cell will recognize each receptor. Cytotoxic T cells recognize that type of MHC that is present on all cells in the body: the type I MHC receptor. It has to be this way, because any cell in the body can become infected, and cytotoxic T cells need to have a way to recognize and kill these cells. Helper T cells, on the other hand, recognize only that type of MHC that is present on antigen presenting cells: the MHC II receptor. Which makes sense, because helper T cells need the cytokines released by antigen presenting cells to help them do their job. So they lock onto the MHC II receptor on antigen presenting cells, and while they’re there, they get nice cytokine signals telling them to grow and differentiate.

Image credit: NIH.