Медицинская иммунология (Jul 2014)
ORIGINS OF ALLOGENEIC RESPONSE
Abstract
Abstract. The MHC molecules are the strongest transplantational antigens determining direct intraction with 95-98% of T cell clones activating in response to allograft. Interaction with MHC molecules is critically important for positive selection of thymocytes and subsequent acquiring the capability to recognize "self" and "foreign". In this light, alloreactivity was recognized as cross-reactivity with foreign MHC that appeared as result of repertoire selection on "self" MHC molecules. The T lymphocyte repertoire is formed in the thymus as a result of random rearrangement of germinal sequences of TCR gene fragments and other processes that bring about the diversity of TCRs. As shown by D. Raulet and co-workers, repertoire of T lymphocytes artificially formed at the absence of selection processes, is inherently capable of reacting with different allelic forms of MHC molecules. In contrast to germinal sequences of TCR fragments, the MHC molecules are characterized by a significant interspecies polymorphism. So, negative and positive selection are aimed at the adaptation of repertoire to the specific MHC-environment of certain individual. The overall goal of adaptation is the elimination of autoreactive clones and sparing a broad spectrum of specificity to potential pathogens. Recent results have shown that positive selection in thymus was result of degenerative recognition of endog- enous MHC/peptide complexes. In contrast, central, telerance to "self" is formed as result of high affinity specific interaction with self MHC/peptide complexes. From this viewpoint the negative selection in the thymus can be considered as a life-long allogenic reaction of repertoire to self MHC molecules; the responses of the mature T cell repertoire to individual antigenic peptides can be considered as cross-reactions of T cells reactive to foreign transplantational antigens. I believe that this interpretation can unveil the origins and biological mean-ingfulness of allogenic reactions.
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