Association between the HLA haplotype and the TCR-Vβ repertoire of anti-hCMV specific memory T-cells in immunocompetent healthy adults

Abstract

[Background]: Despite the key role of memory T-cells specific for human cytomegalovirus (hCMV) in protecting against hCMV-reinfection early after immunodeficiency episodes, the precise characterization and definition of the essential components of a protective CD4 T-cell response still remain to be established. [Methods]: We analyzed by flow cytometry hCMV-specific immune responses driven by peripheral blood antigen-presenting cells (APC) and CD4 memory T-cells at both the cellular and soluble levels, and their cooperation in priming and sustaining the effector function of specific CD8 T cells in adult healthy individuals using a hCMV whole viral lysate stimulatory model. [Results]: Overall, activated T-cells showed a heterogeneous phenotype, with a marked predominance of CD45RA-/CCR7+/- memory CD4+ T-cells. Despite this, cytoplasmic expression of granzyme B was found in both the CD45RA+/effector and CD45RA-/memory T-cell compartments of the two major CD4+ and CD8+ activated T-cell subpopulations, further confirming the presence of circulating antigen experienced cytotoxic CD4+ T cells in hCMV-seropositive individuals. Moreover, we observed that both CD4+ and CD8+ hCMV-specific T-cells included relatively restricted numbers of TCR-Vβ family members. Interestingly, we found a significant association between some HLA Class II and Class I haplotypes and the presence of specifically expanded TCR-Vβ clones of anti-hCMV T cells. [Conclusions]: These results indicate that hCMV-specific memory T-cells are phenotypically heterogeneous, their TCR-Vβ repertoire shaped through the interaction between hCMV epitopes and the HLA haplotype. © 2007 Clinical Cytometry Society.