Unlikely we can say exactly. Intermediary forms of living beings were deserted in evolution, though. So, we have not possibility to discuss this issue with confidence. Beta chains of MHC class II molecules show some homology with heavy chains of MHC class I. Some similarity can be seen between beta-2-microglobulin and alpha-chains of MHC class II. I think, both types of MHC molecules are primarily recognized via interaction of TCRs with "kink-region" in alpha-2 domain of MHC class I or in beta-chain of MHC class II molecules. Here is my reference to these issue: http://www.ncbi.nlm.nih.gov/pubmed/15678685

Sorry! Full text in Russian. Shortly, in this work I checked the presence of common motifs in MHC class I molecules of many different organisms, whose sequences I could find in GenBank. In placental mammals there is strong similarity of these molecules. Great number of coinciding aminoacid residues in the same positions form motifs. Common motifs can be detected even if compare human and shark molecules, but shark MHC class I molecules are at some extent more "compact". On the contrary, alpha and beta chains of MHC class II molecules show great variability in length. Nevertheless, knowing spectra of "allowed" aminoacide substitutions in each position of MHC class I molecules, it is possible "to align" them with MHC class II molecules. In "solid residual" I have seen similarity between AA154-164 of mouse MHC class I, AA63-73 in A-beta and AA69-79 in E-beta chains. Dendrimeric peptides containing these sequences increased the percent of CD3 positive T cells in FTOCs.

That is a good point. At September 2013, I heard Professor Abul K Abbas in a lecture class that when the first organism was documented for HLA, the HLA genes was already done as they are at the present. He also told that is an example of genes that do not follow the idea of evolution. Intriguing !

I would imagine that the MHC II class would have appeared first, as this occurs between macrophages and dendritic cells. B and T lymphocytes, the adaptive immne system, devleloped after innate immunity (non-Specific). T cells, being part of the adaptive immune sytem, operate on the MHCI system, after being primed by and MHC II cell, b lymphocytes, dendritic cells. However, I dont know if all nucleated cells always presented MHC I on the membrane before the adaptive immune system developed. A very interesting question as well.

It could be either one but I'd say MHC I becuase there are MHC I like molecules outside the MHC region and some do not even bind peptides (http://www.ncbi.nlm.nih.gov/pubmed/22001201)

Unlikely we can say exactly. Intermediary forms of living beings were deserted in evolution, though. So, we have not possibility to discuss this issue with confidence. Beta chains of MHC class II molecules show some homology with heavy chains of MHC class I. Some similarity can be seen between beta-2-microglobulin and alpha-chains of MHC class II. I think, both types of MHC molecules are primarily recognized via interaction of TCRs with "kink-region" in alpha-2 domain of MHC class I or in beta-chain of MHC class II molecules. Here is my reference to these issue: http://www.ncbi.nlm.nih.gov/pubmed/15678685

Sorry! Full text in Russian. Shortly, in this work I checked the presence of common motifs in MHC class I molecules of many different organisms, whose sequences I could find in GenBank. In placental mammals there is strong similarity of these molecules. Great number of coinciding aminoacid residues in the same positions form motifs. Common motifs can be detected even if compare human and shark molecules, but shark MHC class I molecules are at some extent more "compact". On the contrary, alpha and beta chains of MHC class II molecules show great variability in length. Nevertheless, knowing spectra of "allowed" aminoacide substitutions in each position of MHC class I molecules, it is possible "to align" them with MHC class II molecules. In "solid residual" I have seen similarity between AA154-164 of mouse MHC class I, AA63-73 in A-beta and AA69-79 in E-beta chains. Dendrimeric peptides containing these sequences increased the percent of CD3 positive T cells in FTOCs.

I also agree with Pedro Reche, and I would also imagine MHC class I molecules, because nonclassical MHC class I molecules are outside the MHC region, and even bind lipids.

Thank you Dmitry. Do the data you mention support one hypothesis rather than the other? And are there data from the comparison of CD4 vs. CD8 that can be used in this issue?

Joachim, the paper you mention on Botryllus is on a molecule not related to vertebrate MHC, and actually turned out not to be involved in histocompatibility either. Thanks to the others for their suggestions.

Dear Daniel, my data support both hypotheses and I can not prefer one of two. In any case, recognition by T cells is closely related for both types of molecules. There are significant differences in development of CD4 and CD8 T cells. At first, developing thymocyte try to recognise MHC class II molecule, During DP developmental stage only CD4 really works as coreceptor, providing lck. Then, more stable interaction of any TCR with MHC class II molecule will result in commitment to CD4 lineage. Less stable interactions will result in development of CD8 cells by default. It seems, this sequence of events results in "more strong" selection of CD4 T cell repertoire than CD8 (promisquous TCRs capable to interact with both MHC class I and II molecules are not detected in peripheral CD4 pool, but represent significant part of peripheral CD8 T cells). If ontogenesis really recapitulates phylogenesis, it may be expected, that MHC class II molecules are more ancient, than MHC class I. However, I should stress that this is pure speculation.

Without answering the question, a very interesting publication in Nature about cod genome sequencing (Nature 477, 207–210 (08 September 2011) doi:10.1038/nature10342had) have shown that cod have lost the MH-II molecules, along with CD4 and li. Nevertheless, theses animals deal perfectly with pathogens, because they had expanded their MHC-I and TLR genes.

Thank you Veronique. Yes, I have seen this fascinating result, but this does not answer the question of which molecules came first.

Most mammals have MHC variants similar to those of humans, who bear great allelic diversity, especially among the nine classical genes.. The most diverse loci, namely HLA-A, HLA-B, and HLA-DRB1, have roughly 1000, 1600, and 870 known alleles, respectively. Many HLA alleles are ancient, sometimes of greater homology to a chimpanzee MHC alleles than to some other human alleles of the same gene.

MHC allelic diversity has challenged evolutionary biologists for explanation. No single allele is absolutely most fit,

Pathogenic co-evolution, a counter-hypothesis, posits that common alleles are under greatest pathogenic pressure, driving positive selection of uncommon alleles—moving targets, so to say, for pathogens. As pathogenic pressure on the previously common alleles decreases, their frequency in the population stabilizes, and remain circulating in a large population. Despite great MHC polymorphism , any individual bears at most 18 MHC I or II alleles.

Even if this is so , it is very difficult to say which MHC ckass evolved first ! At least to me .

As far as I know most evidences support the hypothesis that the ancestral MHC molecules has a class-II like structure and it gave rise to the class-I molecule.

I think , at the moment it is difficult to say which class of MHC got evolved first ! There are lot of arguments and counter arguments which confuses me a lot ! The real answer may come up as the Science will advance.

Eu tenho uma teoria,eu acho que não existe evolução sem uma adaptação do sistema imune no qual envolve uma nova conformação das moléculas HLA , os seres só sobrevivem se essa adaptação for bem sucedida , então ao meu ver qual a molécula MHC surgiu primeiro vai depender de qual foi funcional para a evolução desses seres vivos.

I have a theory, I think there is no evolution without an adaptation of the immune system that involves a new conformation of HLA molecules, beings only survive if this adaptation is successful, then in my view which the MHC molecule came first depends of which was functional for the evolution of living beings.

Thank you Sandip, do you have references?