T Cell Repertoire: Genomic or Somatic Bias Toward Recognition of Major Histocompatibility Complex Molecules?

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Abstract
The prevailing concept about a major influence of thymic positive selection on shaping the T cell repertoire during ontogeny is confronted with an old idea emphasizing a dominant role for genetic (evolutionary) factors in molding the recognition potential of mature T cells. Our recent results are not readily interpreted without introducing a new version of the old concept, according to which complementarity to the major histocompatibility complex peptide-binding site is a major evolutionary selective pressure on T cell antigen receptor variable genes, with alloreactivity being a reflection of this fact.