Contribution of T-cell receptor repertoire breadth to the dominance of epitope-specific CD8+ T-lymphocyte responses.
Dominant epitope-specific CD8(+) T-lymphocyte responses play a central role in controlling viral spread. We explored the basis for the development of this focused immune response in simian immunodeficiency virus (SIV)- and simian-human immunodeficiency virus (SHIV)-infected rhesus monkeys through the use of two dominant (p11C and p199RY) and two subdominant (p68A and p56A) epitopes. Using real-time PCR to quantitate T-cell receptor (TCR) variable region beta (Vbeta) family usage, we show that CD8(+) T-lymphocyte populations specific for dominant epitopes are characterized by a diverse Vbeta repertoire, whereas those specific for subdominant epitopes employ a dramatically more focused Vbeta repertoire. We also demonstrate that dominant epitope-specific CD8(+) T lymphocytes employ TCRs with multiple CDR3 lengths, whereas subdominant epitope-specific cells employ TCRs with a more restricted CDR3 length. Thus, the relative dominance of an epitope-specific CD8(+) T-lymphocyte response reflects the clonal diversity of that response. These findings suggest that the limited clonal repertoire of subdominant epitope-specific CD8(+) T-lymphocyte populations may limit the ability of these epitope-specific T-lymphocyte populations to expand and therefore limit the ability of these cell populations to contribute to the control of viral replication.
Manuel
Edwin R
ER
Beth Israel Deaconess Medical Center, 41 Ave. Louis Pasteur, Boston, MA 02115, USA. nletvin@bidmc.harvard.edu
Charini
William A
WA
Sen
Pritha
P
Peyerl
Fred W
FW
Kuroda
Marcelo J
MJ
Schmitz
Jörn E
JE
Autissier
Patrick
P
Sheeter
Dennis A
DA
Torbett
Bruce E
BE
Letvin
Norman L
NL
D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D019674:Genes, T-Cell Receptor beta / Q000235:genetics; D007111:Immunity, Cellular / Q000276:immunology*; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015302:Simian Immunodeficiency Virus / Q000276:immunology*
D017931:DNA Primers; D018076:DNA, Complementary; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D011948:Receptors, Antigen, T-Cell