Is there a well established explanation for the phenomena that graft-vs-host is so much more selective against phylogenetically close cells? See historically significant references below,

"This type of aggression of the immune system is thus particularly directed against allo-antigens and is much less in evidence across two animals species. “ - Jerne, 1971

"Normal lymphoid cells obtained from animals that are phylogenetically unrelated or only distantly related to the chicken do not initiate graft versus host reactions when introduced into chicken embryos. " - Lafferty, 1968


Lafferty, K., & Jones, M. (1969). REACTIONS OF THE GRAFT VERSUS HOST (GVH) TYPE. Australian Journal of Experimental Biology and Medical Science, 47(1), 17–54. https://doi.org/10.1038/icb.1969.3

Jerne, N. K. (1971). The somatic generation of immune recognition. European Journal of Immunology, 1(1), 1–9. https://doi.org/10.1002/eji.1830010102


Since this has gone unanswered, I'll give my best guess. My guess is that closely related MHC* can still be recognized by CD4/CD8 (while not in distant relatives phylogenetically), but, the MHC + eventual bound peptide will not be recognized as self (with or without bound peptide), since its structure may differ even when binding self-antigen peptides that were exposed to T-cells during central tolerance "traning".

I am very intersted in what the established explanation is including references, and invite better answers if there is competence to produce that.

*in the context of the question, i.e., at species level, within species sufficiently close MHC genes are not attacked at all and compatible.

I'll attach potential reference to my guess that ability to recognize MHC as... MHC, decreases with phylogenetic distance,

Vignali, D. A., Moreno, J., Schiller, D., & Hämmerling, G. J. (1992). Species-specific binding of CD4 to the beta 2 domain of major histocompatibility complex class II molecules. Journal of Experimental Medicine, 175(4), 925–932. https://doi.org/10.1084/jem.175.4.925

that references this,

Lamarre, D., Ashkenazi, A., Fleury, S., Smith, D., Sekaly, R., & Capon, D. (1989). The MHC-binding and gp120-binding functions of CD4 are separable. Science, 245(4919), 743–746. https://doi.org/10.1126/science.2549633

that says this,

"although human and mouse CD4 share a high degree of amino acid sequence identity (19), the murine homolog does not bind gpl20 (11) and does not interact with the human class II MHC molecule HLA-DP as assessed by functional and adhesion assays (20). "


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