Do HLA genes play a prominent role in determining T cell receptor V alpha segment usage in humans?
Previous studies in humans have demonstrated that HLA genes can profoundly influence the TCR V beta repertoire. To similarly assess the influence of HLA genes on the TCR V alpha segment repertoire, the V alpha repertoires of 12 individuals from three unrelated families were determined by quantitative PCR. Each family contained at least one pair of HLA-identical and -nonidentical siblings. Repertoire analysis was performed on purified CD4+ and CD8+ cells by using V alpha-specific primers. We were unable to demonstrate more similar V alpha repertoires between HLA-identical siblings than between HLA-nonidentical siblings. In contrast, when a similar analysis was performed on the same individuals for the V beta repertoire, HLA-identical siblings were found to have significantly more similar repertoires than HLA-nonidentical siblings. Furthermore, both the V alpha and V beta repertoires of monozygotic twins showed striking similarity. Despite our inability to show an influence of HLA genes on the V alpha repertoire, we did observe a very strong skewing in terms of preferential expression on CD4+ or CD8+ cells of several V alpha segments, notably TCRAV1, -2, -5, -6, -7, -11, -12, and -13. These studies suggest that HLA genes play less of a role in determining V alpha segment usage than V beta. Nevertheless, the pronounced skewing of V alpha segment expression in the CD4+ or CD8+ populations suggests some role for HLA genes in determining the V alpha TCR repertoire. Furthermore, the striking similarity of V alpha repertoires of identical twins suggests a major role for non-HLA genes in determining the V alpha repertoire.
Gulwani-Akolkar
B
B
Departments of Medicine, North Shore University Hospital, Cornell University Medical College, Manhasset, NY 11030, USA.
Shi
B
B
Akolkar
P N
PN
Ito
K
K
Bias
W B
WB
Silver
J
J
D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D008285:Major Histocompatibility Complex; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D014430:Twins, Monozygotic
D017931:DNA Primers; D006680:HLA Antigens; D012333:RNA, Messenger