Studies are being carried out to determine the influence of major histocompatibility complex (MHC) genes/gene products (HLA antigens) on disease progression and outcome in individuals infected with retroviruses. The cohorts infected with HIV-1 consist of 2 groups: homosexual men and hemophiliacs. The HLA phenotype of individuals in these cohorts was determined by two methods: serology, which identifies the allelic products of the genes at the various loci, and allele specific oligonucleotides (ASO), which identifies the various alleles at the DNA level. Certain HLA phenotypes, as determined by serologic methods, were elevated in frequency in 77 individuals with the diagnosis of Kaposi's sarcoma, relative to controls consisting of HIV-1 seropositive individuals without disease (462 homosexual men). In analysis of disease progression defined by years from seroconversion to decline of CD4+ cells below 20%, individuals with HLA-DR1 had more rapid disease progression relative to individuals without this phenotype, while CD4+ cell loss was less rapid in individuals with the HLA-DR7 antigens. HLA typing at the DNA level is capable of delineating more extensive allelic polymorphisms than those detected by serology. Using polymerase chain reaction technology, consensous primers, and ASO probes, the distribution of 8 alleles at the DQ-alpha locus and 13 alleles of DQ-alpha were determined in the HIV-1-infected homosexual male populations. Several new techniques and strategies for HLA DNA typing have been developed. A method for delineating the various alleles (and potential new alleles) was developed using single-strand conformational polymorphism. Heteroduplex formation of amplified alleles was found to be capable of discriminating non- MHC identity not detected by serology. A technique for DNA HLA typing was developed using serum and plasma as source materials.
