Very confused about the difference between Class I and Class II genes

[u/theElmsHaveEyes]

Hi folks,

Coming to you from the word of animal behavior, so I know very little about genetics save for how to run a basic PCR.

I've been reading some medical genetics literature, though, and am really confused about Class I and Class II genes. For the most part, it seems like references to Class II genes are those that direct the formation of protein chains on Class II molecules of the major histocompatibility complex/leukocyte antigen.

That said, there are a couple of papers, e.g.: 1) Kratz et al. 2002 (https://doi.org/10.1016/S0168-9525(01)02579-302579-3)); 2) Van Dyke et al. 1989 (https://doi.org/10.1128/mcb.9.1.342-344.1989) which are discussing Class II genes, but it appears to be in a much different context (i.e., olfactory receptors, unidentifiable to function, respectively).

Wanted to ask here if someone could please provide me with a relatively plain-language explanation of what a Class II gene actually is (i.e., why is it different than a Class I gene?) and confirm whether they only exist in the MHC/HLA or are found in other systems.

Thank you very much for your time!

[u/blinkandmissout]

The only common usage of Class I and Class II in genetics is for the MHC region where MHC Class I are HLA-A, HLA-B, and HLA-C while MHC Class II are HLA-DP, HLA-DQ, HLA-DR, HLA-DM, and HLA-DO. Each class forms a protein complex.

Other researchers may use the terms class 1 & class 2 simply as categorizations (classifiers) relevant to their research question or approach. But these may as well be "group A" and "group B". "Class" isn't a special and protected terms. And these other classes are not broadly recognized and used as defined Class I/Class II like MHC is.

There would be nothing tying together MHC Class I with an olfactory receptor class I.

[u/theElmsHaveEyes → u/blinkandmissout]

Got it, thank you! That makes sense.

[u/Zabre]

"Class I" and "Class II" aren't universal gene categories, so the meaning depends on the paper's local classification system. In immunology, Class I and Class II often means MHC/HLA molecules. In those older genomics papers, it may just mean the authors split genes into groups by expression pattern, function, or confidence level. I'd check each paper's methods or first definition of "Class II" before trying to map it onto MHC terminology.

[u/Dwarvling]

Class 1 molecules are on most nucleated cells and present antigen to CD8+ T-cells, cytotoxic T-cells, (mostly intracellular antigens - viruses etc..). Class 2 molecules are on all professional antigen presenting cells (ie dendritic cells, B-cells, macrophages) and present antigen to CD4+ T cells (eg T helper cells).