LIMITED RESTRICTION IN THE TCR-ALPHA-BETA-V-REGION USAGE OF ANTIGEN-SPECIFIC CLONES - RECOGNITION OF MYELIN BASIC-PROTEIN (AMINO-ACIDS-84-102) AND MYCOBACTERIUM-BOVIS 65-KDA HEAT-SHOCK PROTEIN (AMINO-ACIDS-3-13) BY T-CELL CLONES ESTABLISHED FROM PERIPHERAL-BLOOD MONONUCLEAR-CELLS OF MONOZYGOTIC TWINS AND HLA-IDENTICAL INDIVIDUALS
Ge. Hawes et al., LIMITED RESTRICTION IN THE TCR-ALPHA-BETA-V-REGION USAGE OF ANTIGEN-SPECIFIC CLONES - RECOGNITION OF MYELIN BASIC-PROTEIN (AMINO-ACIDS-84-102) AND MYCOBACTERIUM-BOVIS 65-KDA HEAT-SHOCK PROTEIN (AMINO-ACIDS-3-13) BY T-CELL CLONES ESTABLISHED FROM PERIPHERAL-BLOOD MONONUCLEAR-CELLS OF MONOZYGOTIC TWINS AND HLA-IDENTICAL INDIVIDUALS, The Journal of immunology, 154(2), 1995, pp. 555-566
We have analyzed the TCR-alpha beta repertoire specific for a given pe
ptide/MHC complex by using pairs of HLA-identical individuals ranging
from monozygotic twins to unrelated individuals to examine the contrib
ution of genetic background and HLA expression in shaping the potentia
l response to a single antigenic epitope. This panel has been previous
ly defined, demonstrating that the concordance of the peripheral TCR-a
lpha beta repertoires directly correlates to the level of relation and
HLA identity. We have analyzed peptide-specific T cell clones derived
from T cell lines from these individuals specific for MHC class II-re
stricted peptides: Mycobacterium bovis 65-kDa heat shock protein (65-k
Da hsp) amino acids (aa) 3-13 (DR3-restricted), and myelin basic prote
in aa 84-102 (DR2-restricted). DNA sequence analysis was used to deter
mine the composition of the TCR-alpha beta V regions. Although the ove
rall TCR-alpha beta repertoires between individuals were diverse, an i
ntra-individual limited restriction was evident. There was also a limi
ted conservation in the response to the different peptides: high frequ
encies of V beta 2, 4, 7, 19, V alpha 21, and J alpha 17 responded to
the MBP aa84-102, whereas these V/J regions were limited or absent in
the 65-kDa hsp aa3-13 repertoire. Similarly, V beta 5.1 and J alpha 9
were increased in the 65-kDa hsp aa3-13 repertoire. Within the CDR3s,
motifs could be identified that were similar between twins. Furthermor
e, one of these motifs resembled CDR3s previously found in correspondi
ng animal models. Similarities could also be seen in the CDR3s of T ce
ll clones sharing V gene usage and peptide specificity. Thus, the in v
itro response to antigenic peptides seems to be quite heterogeneous ov
erall and individual specific.