The main goal of this project is to examine the regulation of expression and function of the mouse T lymphocyte differentiation antigen L3T4. L3T4 is expressed predominantly by helper/inducer T cells and these cells play a critical role in regulating immune responses. It is this population which is eliminated or reduced in acquired immune deficiency syndrome (AIDS). Furthermore, T4, the human homolog of L3T4 is the receptor for the retrovirus which causes AIDS, human T- lymphotropic virus type III. The organization and nucleotide sequence of the L3T4 gene will be determined using previously isolated genomic clones. Sequences involved in regulating the level of expression of this gene and in determining the tissue specificity of expression will be analyzed both by transfection experiments into tissue culture cells and by the generation of transgenic mice. The role of L3T4 in T cell recognition processes will be examined by transfection of the gene into Lyt-2+ functional T cells and by generation of transgenic mice which express L3T4 on inappropriate T cells. The function will be further investigated by the use of anti-sense RNA to block expression of the protein in functional T cells. Gene constructs which produce anti-sense RNA will also be used to examine the necessity for L3T4 on T cell clones which induce experimental allergic encephalomyelitis. The expression of L3T4 by brain will be investigated and the difference(s) between the L3T4 mRNA species found in T cells and a unique species found in brain will be determined by isolation and sequencing of brain cDNA clones which hybridize to L3T4 probes. The specific cells in brain which express L3T4 at the protein and mRNA levels will be determined by immunoperoxidase staining and in situ hybridization. These studies of expression in brain may have important implications for the central nervous system involvement in AIDS.