Association between the HLA haplotype and the TCR-Vbeta 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-Vbeta family members. Interestingly, we found a significant association between some HLA Class II and Class I haplotypes and the presence of specifically expanded TCR-Vbeta clones of anti-hCMV T cells.

Conclusions: These results indicate that hCMV-specific memory T-cells are phenotypically heterogeneous, their TCR-Vbeta repertoire shaped through the interaction between hCMV epitopes and the HLA haplotype.