The helper T-cell repertoire of mice expressing class II major histocompatibility complex β chains in the absence of α chains

1432-1211

Springer Online Journal Archives 1860-2000

Biology

Medicine

Abstract  Mutant mice generated by disrupting the H2-Aa b major histocompatibility complex (Mhc) gene are demonstrated here to express Aβb chains in the absence of α chains. These mice possess a CD4+ helper T cell (Th) repertoire that uses predominantly the Vβ7 T-cell antigen receptor (Tcr) segment for recognition of any protein antigen presented by the α-free Aβ molecule. As an alloantigen, the Aα-free Aβ molecule is recognized very poorly by T cells from a series of class II disparate mouse strains, indicating that it is grossly different from normal α/β heterodimers. Indeed, molecular modeling suggests a β/β homodimer arrangement with an altered geometry of the Tcr contact area. Interestingly, the mutant mice exhibit normal alloreactivity, without a restricted Vβ usage, toward a series of foreign α/β class II heterodimers, although their T cells developed in the absence of such heterodimers. Thus, the complementarity of Tcr to normal α/β heterodimers, and thereby also alloreactivity, appears to be an ontogeny independent (i. e., germline-encoded) feature.

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