Experiments are proposed to investigate T cell responses in HIV infected individuals with the diffuse infiltrative lymphocytosis syndrome (DILS). This syndrome is strongly associated with HLA-DR5 (RR=35) in the black population. The preliminary hypothesis to be investigated is that DR5 haplotypes confer a high responder phenotype for HIV envelope specific T cell responses, thereby predisposing to the development of DILS. At least 4 distinct DR5 alleles have been defined by DNA sequence analysis; preliminary analysis indicates that certain of these DR5 alleles may be specifically associated with DILS. The proposed studies are contained in 4 specific aims:
specific aim 1) confirm and extend ongoing studies concerning which subtypes of DR5 are associated with DILS;
specific aim 2) establish the level of T cell responsiveness to HIV envelope antigens (gp160) in patients with DILS;
specific aim 3) develop gp 160 specific, class II restricted T cell clones derived from the bulk T cell responses identified in specific aim 2. The precise MHC restriction patterns of these T cells clones will be defined using homozygous typing cells as well as by monoclonal antibody blocking studies. In addition, Ia- cell lines transfected with individual class II alleles will be used as antigen presenting cells for these studies.
Specific aim 4) identify and compare the immunodominant epitopes of gp160 presented by DR5 and non DR5 alleles. These studies will provide an opportunity for detailed study of the influence of well defined class II polymorphisms on antigen specific T cell recognition, as well as provide insight into the role of MHC polymorphisms in the pathogenesis of DILS.
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