AEGiS-05CROI: Analysis of TCR repertoire against a conserved HIV-RT CTL epitope in a cohort of HIV+ patients.

5th Conference on Retroviruses and Opportunistic Infections


Chicago, IL - February 1-5, 1998



Analysis of TCR repertoire against a conserved HIV-RT CTL epitope in a cohort of HIV+ patients.

Conf Retroviruses Opportunistic Infect 1998 Feb 1-5; 5th:82 (abstract no. 17)

Kolowos W, Bachmann O, Schmitt M, Herrmann M, Goldwich A, Baurle M, Low P, Harrer E, Kalden JR, Harrer T; Department of Medicine III, University of Erlangen-Nurnberg, Germany.

OBJECTIVE: To analyze the TCR-repertoire against a conserved epitope in a cohort of HIV-infected patients and to study whether expansion of HIV-specific CTL clones contributes to disruption of T-cell receptor repertoire in HIV+ patients.

METHODS: By stimulation of PBMC from HIV-1 infected HLA A2 + patients with the RT peptide ILKEPVHGV (IV9) we generated IV-9 specific CTL lines from 11 patients. Functional characterization of TCRs was done by testing CTL for recognition of variant peptides. In addition, CDR3 regions of alpha- and beta-chains of TCRs of several CTL lines were sequenced. T-cell receptor repertoire analysis of PBMC from the patients was done by TCR spectratyping.

RESULTS: Analysis of the functional recognition pattern of amino acid substitutions in the epitope revealed the presence of at least four different TCRs in the population, and in several subjects the presence of at least two different CTL clones with different epitope specific TCRs. Molecular analysis of three CTL clones with the same functional specificity revealed highly related TCRs with usage of both Vbeta6.1 and Valpha2 and only minor differences in the CDR3 regions. TCR-speckatyping of PBMC showed in two patients a strong expansion of an individual TCR within the vbeta6.1 family which had the identical sequence as isolated iv-9 specific CTL clones from the same patients.

CONCLUSION: The immune system can mount a broad repertoire of TCRs against this conserved epitope. Patients show important differences in the quality of TCRs with regard to recognition of viral variants. The disruption of TCR-repertoire in HIV infected patients is, at least partially, caused by the expansion of HIV-specific CTL.

Keywords: AEGIS, Receptors, Antigen, T-Cell, Epitopes, HLA-A2 Antigen, HIV-1, Complementarity Determining Regions, Clone Cells, HIV-1 Reverse Transcriptase, Peptides, CDR3 region, Human, analysis, AIDSKWDaegis,receptors,antigen,t-cell,epitopes,hla-a2antigen,hiv-1,complementaritydeterminingregions,clonecells,hiv-1reversetranscriptase,peptides,cdr3region,human,analysis,aids

1998-02-01
17

Copyright © 1998 - Foundation for Retrovirology and Human Health (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed from National Library of Medicine.