Structure of MHC class I and class II cDNAs and possible immunodeficiency linked to class II expression in the Mexican axolotl

Despite the fact that the axolotl (Ambystoma spp. a urodele amphibian) disp lays a large T-cell repertoire and a reasonable B-cell repertoire, its humo ral immune response is slow (60 days), non-anamnestic, with a unique IgM cl ass. The cytotoxic immune response is slow as well (21 days) with poor mixe d lymphocyte reaction stimulation. Therefore, this amphibian can be conside red as immunodeficient. The reason for this subdued immune response could b e an altered antigenic presentation by major histocompatibility complex (MH C) molecules. This article summarizes our work on axolotl MHC genes. Class I genes have been characterized and the cDNA sequences show a good conserva tion of non-polymorphic peptide binding positions of the a chain as well as a high diversity of the variable amino acids positions, suggesting that ax olotl class I molecules can present numerous antigenic epitopes. Moreover, class I genes are ubiquitously transcribed at the time of hatching. These c lass I genes also present an important polylocism and belong to the same li nkage group as the class II B gene; they can be reasonably considered as cl assical class Ia genes. However, only one class II B gene has been characte rized so far by Southern blot analysis. As in higher vertebrates, this gene is transcribed in lymphoid organs when they start to be functional. The se quence analysis shows that the peptide binding region of this class II beta chain is relatively well conserved, bur most of all does not present any v ariability in the pi domain in inbred as well as in wild axolotls, presumin g a limited antigenic presentation of few antigenic epitopes. The immunodef iciency of the axolotl could then be explained by an altered class II prese ntation of antigenic peptides, putting into question the existence of cellu lar co-operation in this lower vertebrate. It will be interesting to analyz e the situation in other urodele species and to determine whether our obser vations in axolotl represent a normal feature in urodele amphibians. But al ready two different models in amphibians, Xenopus and axolotl, must be cons idered in our search for understanding immune system and MHC evolution.