The analysis of 650 HLA-A:HAL-B:Bf three-factor haplotypes revealed significant associations only between alleles of the very closely linked genes HLA-A and HLA-B, and Bf, respectively. Most striking is the highly significnat association of the rare Bf variant F1 with HLA-B18 and of S1 with HLA-B13, HLA-B14, and HLA-Bw21. Only random allele distributions were observed when considering the somewhat more distant genes HLA-A and Bf or the higher order interaction at all three genes. From these findings it seems likely that the linkage disequilibrium within the MHC is not due to selective forces, but rather due to a short evolutionary period.
Delineation of major T helper cell recognition sites of human immunodeficiency virus (HIV-1) proteins represents one important step in the design of an efficient acquired immune deficiency syndrome (AIDS) vaccine. Towards this end, we have explored the immunogenicity of HIV-1BRU proteins in the mouse model. Preliminary experiments revealed that inbred mice primed with whole inactivated HIV-1 developed strong CD4+ T cell proliferative responses to a variety of recombinant viral proteins including reverse transcriptase (RT). To characterize further the mouse T cell responses to this protein, several Ad- or Ed-restricted T hybridoma cells (THC) were established from BALB/c or DBA/2 mice. These THC were tested for their capacity to recognize a series of 15-mer synthetic overlapping peptides spanning three segments of HIV-1 RT that had been preselected on the basis of either alpha-helicity, amphipaticity, and/or for containing rare amino acid sequence patterns. Peptides corresponding to a C-terminal region (residues 528-560) of RT were recognized by several of the THC established from RT-primed mice. Furthermore, a non-alpha-helical peptide from this region (A3, 528-543) was capable of priming mice with different H-2 haplotypes for both peptide A3 and native RT CD4+ T cell recognition. In addition to the recently identified RT determinant 203-219 capable of triggering both mouse and human CD8+ CTL, the present results identify a good candidate for an immunodominant RT epitope capable of eliciting RT-specific T helper cell responses.
The newly described genetic polymorphism of glyoxalase I (GLO) is studied in seven ethnically defined Negroid samples from South Africa (total: n = 843). The allele frequencies between the different Negroid samples studied vary only marginally. However, the allele frequency of GLO1 for the South African Negroid samples combined (i.e., p = 0.259), is highly significantly lower than that for Caucasoid samples.
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