Recognition of polymorphic H-2 domains by T lymphocytes. I. Functional role of different H-2 domains for the generation of alloreactive cytotoxic T lymphocytes and determination of precursor frequencies.

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Abstract
The repertoire of mouse alloreactive cytotoxic T lymphocyte (CTL) clones was quantitatively investigated by limiting dilution analysis and by target inhibition with a panel of monoclonal antibodies (mAb). These mAb were previously shown to define 2 distinct alloantigenic domains, A and B, on the H-2Kk molecule. The Poisson distribution analysis of H-2Kk-specific CTL clones generated in a limiting dilution system revealed 3 CTL populations with different precursor frequencies. The most frequent population is suppressed by an unknown suppressive mechanism that allows less frequent CTL populations to become visible. Target inhibition studies with a panel of Kk-specific mAb showed that these CTL populations differ in their precursor frequency and their specificity for different H-2 epitopes on the Kk molecule. Thus, clones of the high frequency population are almost exclusively specific for determinants within domain A. The low frequency population displays predominant specificity for determinants of domain B. The population with medium frequency is blocked equally well by mAb against either domain. Each mAb blocked only a fraction of clones, indicating that each CTL subpopulation may consist of a large number of clonotypes with specificity for different H-2 epitopes. Evidently CTL recognize basically the same polymorphic domains on the H-2Kk molecule defined by antibodies, and regulatory mechanisms determine the expressed repertoire in CTL populations.