HUMAN T-CELL REPERTOIRE GENERATION IN THE ABSENCE OF MHC CLASS-II EXPRESSION RESULTS IN A CIRCULATING CD4(-) POPULATION WITH ALTERED PHYSICOCHEMICAL PROPERTIES OF COMPLEMENTARITY-DETERMINING REGION-3()CD8()
J. Henwood et al., HUMAN T-CELL REPERTOIRE GENERATION IN THE ABSENCE OF MHC CLASS-II EXPRESSION RESULTS IN A CIRCULATING CD4(-) POPULATION WITH ALTERED PHYSICOCHEMICAL PROPERTIES OF COMPLEMENTARITY-DETERMINING REGION-3()CD8(), The Journal of immunology, 156(3), 1996, pp. 895-906
In this study, we have investigated the impact of deficient MHC class
II expression on the use of TCRBV6 and TCRBJ gene elements, and on the
pattern of amino acid incorporation exhibited in the N1-D-N2 segments
of the third complementarity-determining region (CDR3) of these TCRBV
6 rearrangements, To this end, we have analyzed circulating T cells fr
om three, nonrelated MHC class II-deficient (bare lymphocyte syndrome
(BLS)) patients and three MHC class II-expressing family members, The
patients and healthy controls exhibited similar, nonrandom usage profi
les of TCRBV6 and TCRBJ gene elements in both the CD4(+)CD8(-) and the
CD4(-)CD8(+) subsets of peripheral blood T cells, No statistically si
gnificant differences between patients and controls were detected in t
he length of CDR3, or in the amount of non-germline modification at th
e sites of recombination. However, detailed analysis of the TCRBV6 rea
rrangements derived from the CD4(+)CD8(-) subsets from the BLS patient
s revealed patterns of amino acid incorporation into the N1-D-N2 regio
n of CDR3 that resulted in altered charge and hydropathicity propertie
s of the presumed Ag binding site, In this way, we have been able to d
emonstrate that human T cell repertoire development in the absence of
MHC class II expression results in a circulating CD4(+)CD8(-) T cell p
opulation bearing TCRs with altered CDR3 profiles, Such altered profil
es are likely to be a direct reflection of the lack of MHC class II-me
diated selection processes in these BLS patients.