AEGiS-11IAC: Longitudinal analysis of T cell receptor beta chain clonal diversity during acute HIV infection: molecular and cellular approaches.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Longitudinal analysis of T cell receptor beta chain clonal diversity during acute HIV infection: molecular and cellular approaches.

Int Conf AIDS 1996 Jul 7-12; 11:12 (abstract no. We.A.380)
Soudeyns H, Demarest JF, Vaccarezza M, Daucher M, Pantaleo G, Sekaly RP, Fauci AS; Immunologie, IRCM, Montreal, Quebec. Fax: (514) 987-5711.

OBJECTIVES: Patients undergoing acute HIV infection often exhibit transient, high-level TCR Vb-specific expansions of CD8+ T cells. These expanded T cell subsets mediate HIV-specific cytotoxicity, and are believed to be part of the initial immune response to HIV infection. Molecular and cellular analysis were performed in order to characterize the clonality, specificity, and persistence of the response.

METHODS: The TCR b chain was cloned from freshly isolated PBMC samples collected at different time points during primary HIV infection from two HIV-infected individuals. Sequence analysis of the VDJ (CDR3) junction was then performed. Clonal representation in sequential samples was confirmed by diversity-specific PCR (DS-PCR). Antigenic specificity was mapped by using overlapping peptide panels in cytotoxic assays.

RESULTS: In both patients, presence of discrete TCR clonotypes showed the oligoclonal nature of the expanded Vb subsets. Biased Jb usage, restriction of CDR3 length and conservation of CDR3 residues before and after expansion suggested the presence of an antigen-driven selection process. Fine antigenic specificity and kinetics of appearance of amplified clonotypes relative to circulating viremia further indicated that these expansions were virus antigen-driven, and might represent true primary response to HIV-1. Furthermore, rapid and complete disappearance (2 weeks) of specific amplified clonotypes was observed and confirmed by using DS-PCR. Distinct T cell clones with identical peptide specificity were not similarly deleted, and remained detectable in the patient for extended periods.

CONCLUSION: These results suggest that processes such as clonal exhaustion and viral escape mutation might be involved in the disappearance of clonally-amplified HIV-specific cytotoxic T cells. Relative TCR affinities for the peptide-MHC complexes might explain the differences in persistence of HIV-specific T cell clones with identical antigenic specificity.

Keywords: AEGIS, Receptors, Antigen, T-Cell, alpha-beta, Receptors, Antigen, T-Cell, HIV Infections, T-Lymphocyte Subsets, HIV-1, T-Lymphocytes, HIV, Clone Cells, T-Lymphocytes, Cytotoxic, HIV Antigens, Epitopes, Antigens, CD8, HIV Envelope Protein gp41, Polymerase Chain Reaction, Human, analysis, ICA11

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