7
#22
KIR GENE CONTENT AND HIV PROGRESSION.
M.R. Uribe BS 1, S. Adams BS 1, L. Shupert 2, D. Stroncek MD 1, M. Connors MD 2 and F. Marincola MD 1. 1 DTM HLA Lab., NIH, Bethesda, MD, USA and 2 NIAID, NIH .
Several clinical correlations reported point to the importance of the KIR receptors in viral infections. We performed SSP-PCR low resolution KIR genotyping in 48 HIV+ individuals; 26 long term nonprogressors, or slow progressors (LTNP/SP) and 22 progressors(P). Seventy five percent were predetermined to be HLA- B57 (17 LTNP/SP, and 19 P ).HLA typing was performed by low resolution SSP-PCR. Data obtained was analyzed for association with KIR gene content (group A /B haplotypes), and presence of individual activating KIR genes with the corresponding HLA-KIR ligands. We found that 69% of the LTNP/SP had KIR genotypes with two or more stimulatory KIR genes (group B haplotypes), while only 45% of the progressors were in this group (table 1). No significant association was observed with individual activating genes and disease progression (table 2). Since individual NK clones express different activating and inhibitory KIRs, we hypothesize that individuals with several activating KIR genes have a higher probability of expressing them on any given NK cell than individuals with fewer activating KIRs. It is important to perform KIR genotyping at the allele level, since variation in gene content and allelic diversity may affect NK cell function. HLA-B57 allele typing will be informative to elucidate any additional correlation.
| Disease Progression | Group A Haplotypes | Group B Haplotypes | Total |
| LTNP/SP | 8 ( 31%) | 18 (69%) | 26 |
| P | 12 (55%) | 10 (45%) | 22 |
| Total | 20 | 28 | 48 |
Table 1
| Disease Progression | KIR2DS1 | KIR2DS2 | KIR2DS3 | KIR2DS4 | KIR2DS5 | KIR3DS1 |
| LTNP/SP (HLA ligand) | 50% 13/26 (11/13) | 46% 12/26 (11/12) | 23% 6/26 (?) | 88%23/26(1/23) | 42%11/26 ( ? ) | 42% 11/26 (11/11) |
| P (HLA ligand) | 27% 6/22 (5/6) | 36% 8/22 (7/8) | 27% 6/22 (?) | 91%20/22(2/ 20) | 27%6/22 ( ? ) | 27% 6/22 (5/6) |
Table 2