AEGiS-11IAC: T cell antigen receptor and its relation to HIV-1 infection.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

T cell antigen receptor and its relation to HIV-1 infection.

Int Conf AIDS 1996 Jul 7-12; 11:212 (abstract no. Th.A.145)
Hodara V, Jeddi-Tehrani M, Scarlatti G, Esin S, Holmberg V, Libonatti O, Albert J, Wigzell H; Departamento de Microbiologia, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. Fax: 54 1 9625404.

OBJECTIVES: To analyze the specificity of HIV to replicate and kill different CD4 T+ cell populations in vivo.

METHODS: Blood samples from 13 HIV-infected individuals (4 at Centers for Disease Control (CDC) stage II, 5 at CDC stage III and four at CDC stage IV) were obtained and PBMC were isolated by Ficoll-Hypaque gradient. CD4+ and CD8+ cells were separated using anti-CD4 and anti-CD8 antibodies coupled to magnetic beads (Dynal, Norways) to study the TCR repertoire by RT-PCR and hybridization to specific oligonucleotide probes for Cbeta and 13 different Jbetas. MoAb against TCR Vbeta 12 and Vbeta3 were used to enrich specific T cell populations from 2 asymptomatic individuals and, mRNA and DNA were extracted to quantify viral and proviral nucleic acids. To quantify HIV, DNA and cDNA (after reverse transcription using random primers) were amplified by using primers specific for HIV-1 pol region in a nested limiting dilution PCR. mRNA/DNA ratio was calculated.

RESULTS: CD8 and CD4 populations of all individuals at CDC stage II and III showed a full repertoire of TCR considering 20 families of TCR Vbetas and 13 different Jbetas. However, patients at CDC stage IV had shown different repertoires for one of the two populations. Full pattern of V and J regions of the TCR betha chain was seen for the CD8 population but several Vbetas were missing in the CD4 repertoire. The Vbetas present, had a normal usage of the J segments. 3 out of 4 patients showed a hole in the CD4 repertoire for Vbeta families included in region Vbeta9 to Vbeta20. Only Vbeta3 was depleted in both CD4 and CD8 populations. In the early stages of HIV infection, asymptomatic patients had a differential replicative rate showed by the mRNA/DNA ratio for Vbeta12 and Vbeta3 cells. Vbeta12+ T cell population showed a ratio of 40 while Vbeta12- had 0,1. The ratio for Vbeta3+ T cells from the same patient was 1,4 while Vbeta3-cells was 0,04. Another asymptomatic individual showed ratios: 6,2 for Vbeta12, 0,24 for Vbeta12-, 4,4 for Vbeta3+ and 1,1 for Vbeta3-.

CONCLUSIONS: Active replication in specific Vbeta bearing cells can be responsible for the production of clonal proteins with specific superantigenic capacity to subsequently kill specifically certain T cells but not others. Different Vbetas will be compromised during the course of HIV infection, thus the distinct T cells populations would be eliminated as observed at later stages.

Keywords: AEGIS, Receptors, Antigen, T-Cell, HIV Infections, HIV-1, Antigens, CD4, Antigens, CD8, T-Lymphocytes, Polymerase Chain Reaction, Human, ICA11

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