Recent studies have revealed that although the frog, Xenopus, expresses class II molecules throughout larval and adult life, tadpoles of this species do not express detectable class I antigens until they reach metamorphic climax. Hence, the larval frog provides a unique """"""""model of nature"""""""" (somewhat akin to humans with the """"""""bare lymphocyte"""""""" syndrome) with which to examine the biological roles of class I and class II antigens and class I- and class II-reactive T cells from an immunologic, ontogenetic, and phylogenetic perspective. The major goal of this proposal is to better understand the importance, in Xenopus, of class I antigen expression and anti-class I-reactive and class II-reactive T cells on: 1) lymphocyte-target cell interactions, 2) the establishment of self-tolerance and allotolerance, and 3) the ontogeny of the T cell repertoire. More specifically, I will use in vitro proliferative and cytotoxic assays, skin grafting between larvae and adults, embryonically created thymus/hematopoietic chimeras, and molecular biological techniques to address the following questions: 1. During adult life, do class I and class II gene products serve as target and restriction molecules of cytotoxic T cells? 2. In the absence of class I expression, do tadpoles have class I- restricted and anti-alloclass I-reactive cytotoxic T cells? 3. Do class II molecules serve as restriction elements for both helper and cytotoxic T cells of tadpoles? 4. Is there a relationship between the lack of class I expression and the ease with which tadpoles become tolerant of adult skin allografts (i.e., do class II disparities favor tolerance induction)? 5. If expression of class I molecules can be induced precociously in tadpoles, does this accelerate maturation of anti-class I- reactive T cells and facilitate development of autoimmunity? 6. Does the thymus play a critical role in the acquisition of the T cell repertoire, and when during ontogeny does it play this role? 7. What rearrangements of T cell receptor genes occur during ontogeny?
