Structure and function of H-2 T (Tla) region class I MHC molecules

The T region of the mouse major histocompatibility complex (MHC) encodes a relatively large number of nonclassical or nonpolymorphic class I genes. In BALB/c mice, at least five of these genes are likely to encode a functional class I gene product. Some of these T region products are ubiquitously expressed, while others are expressed by just a few tissues. In the second category, the thymus leukemia (TL) antigen, which is encoded in the T region by T3 and T18 genes, is expressed primarily by intestinal epithelial cells and thymocytes. Inspection of the sequences of the alpha 1 and alpha 2 domains, which could encode a peptide binding site in these molecules, indicates that in several cases conserved amino acids important for peptide binding by classical class I molecules are present, suggesting that these nonclassical class I molecules can bind nonamer peptides. On the other hand, analysis of the sequence of the T10d gene product suggests that it can not bind nonamer peptides in a fashion similar to classical class I molecules. Although there are so far no examples of the recognition of defined peptides in the context of T region gene products, there are several examples of T cell recognition of these class I molecules. Both alpha beta and gamma delta T cell receptors are involved in this recognition. Transgenic mice that over express the TL antigen show a variety of abnormalities in thymocyte differentiation and function, providing some support for the hypothesis that this nonclassical class I molecule plays a role in T-cell differentiation. Despite this, the most likely function for T region encoded and other nonclassical class I gene products is a specialized antigen presenting function, perhaps in restricted anatomic sites or to specialized T-cell populations.