Association between the HLA haplotype and the TCR-Vbeta repertoire of anti-hCMV specific memory T-cells in immunocompetent healthy adults.
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.
Rodriguez-Caballero
Arancha
A
Centro de Investigacion del Cancer/IBMCC (CSIC/USAL) and Servicio General de Citometria, Universidad de Salamanca, 37007 Salamanca, Spain.
Garcia-Montero
Andres C
AC
Almeida
Julia
J
Balanzategui
Ana
A
Munoz-Criado
Santiago
S
Orfao
Alberto
A
D000328:Adult; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D007121:Immunocompetence / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology
C515370:CCR7 protein, human; D015704:CD4 Antigens; D016827:CD8 Antigens; D000939:Epitopes; D006680:HLA Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D017493:Leukocyte Common Antigens