Restricted T cell receptor expression by human T cell clones specific for mycobacterial 65‐kDa heat‐shock protein: Selective in vivo expansion of T cells bearing defined receptors

Abstract

We have examined the T cell receptor (TcR) expression of clones specific for epitopes of mycobacterial 65-kDa heat-shock protein (hsp65) in the context of two different HLA molecules, and used this system as a model to assess the selection of T cells responsive to this antigen in vivo. DR3-restricted clones were raised from both the synovial fluid (SF) and peripheral blood (PB) of a patient with reactive arthritis in three separate cloning events. Five of five SF-derived clones tested expressed either V beta 5.2 or a closely related beta chain, V beta 5.6. The alpha chains expressed by V beta 5.2+ and V beta 5.6+ clones were from different families, V alpha 2.4 and V alpha 23.2, respectively. Nine of ten clones derived from two cloning procedures on PB taken 3 years later also expressed either V beta 5.2 or V beta 5.6. This suggests that the TcR repertoire for recognizing this major histocompatibility complex/peptide complex is relatively restricted and favors the use of V beta 5. Conservation of the beta chain third complementarity-determining region (CDR3) sequence was not evident, however. Sequencing alpha and beta chains of representative V beta 5.2+ and V beta 5.6+ PB-derived clones revealed TcR which were identical to those utilized by the SF-derived clones, showing that the repertoire for recognition of this antigen is stable over time. Similar studies of TcR expression were carried out on hsp65-specific, DP4-restricted clones derived from the SF of a patient with rheumatoid arthritis by two independent cloning procedures. There was conservation of alpha chain usage, since all clones expressed a member of the V alpha 1 family, but again CDR3 sequence conservation was not apparent. beta chain usage was not restricted since different clones expressed V beta 6.7, V beta 22.3 and V beta 12. Subtle differences in epitope specificity were detected for two clones with differing TcR. Once more, T cell clones with identical alpha and beta TcR chains were obtained from the separate cloning procedures, suggesting oligoclonalty of T cells with this defined specificity in the patient's SF.

Persistent high frequency of human immunodeficiency virus-specific cytotoxic T cells in peripheral blood of infected donors.

“…The two clones isolated from donor 008 have also persisted for 30 months to date. Previous reports have also documented long-term in vivo persistence of house dust mite-or heat shock protein-specific CD4+ T-cell clones in seronegative donors (26,27).…”

Definition of Five New Simian Immunodeficiency Virus Cytotoxic T-Lymphocyte Epitopes and Their Restricting Major Histocompatibility Complex Class I Molecules: Evidence for an Influence on Disease Progression

“…While there were several differences (8,13,18,19,27), the vast majority of MHC class II-restricted T-cell responses involve products of the more polymorphic HLA-DR and -DQ loci. Therefore, it is unlikely that a single difference at the Mamu-DPB1 locus would account for the dramatic differences in disease progression observed within this family.…”

Limited heterogeneity of biased T‐cell receptor Vβ gene usage in lung but not blood T cells in active pulmonary sarcoidosis

“…[7][8][9][10][11][12][13][14] This approach is based on the knowledge that antigen-specific immune responses can be associated with biases in the usage of specific -chain are seen in antigen-specific T cells specific for cytochrome-c, myelin basic protein, mycobacterial heat shock proteins, influenza virus and tetanus toxoid. [15][16][17][18][19][20][21] Biases in the usage of Va TCR gene segments have also been reported for selected antigen-specific T cells. 22 In these instances, components of the a -or b -chain of the TCR appear to be selected by limited antigenic peptides complexed with MHC class II molecules.…”