Recognition requirements for the activation, differentiation and function of T-helper cells specific for class I MHC alloantigens

The most potent of all T cell-mediated immune responses are those directed against allogeneic major histocompatibility complex-encoded determinants, reflecting the uniquely high frequency of allospecific T cells. Because many allospecific T cells cross-reactively recognize antigenic complexes composed of self-MHC + conventional foreign antigens, it is generally thought that alloreactivity results from the close resemblance between allogeneic MHC determinants and self + X antigenic complexes. While such "antigen mimicry" may explain the high frequency of allospecific T-effector cells, it fails to account for the diversity and specificity of the T-helper mechanisms involved in initiating alloreactions. In this review, the authors will specifically focus on the antigenic requirements for initiating MHC class I-allospecific T-cell responses in vitro and in vivo, with major emphasis on the recognition requirements exhibited by the T-helper cells that initiate such responses.