CHARACTERIZATION OF A THIRD FORM OF THE HUMAN T CELL RECEPTOR y/S

A subpopulation of peripheral blood Tlymphocytes express anovel non-a, non-0 T cell receptor (TCR) heterodimer that is associated with the CD3 complex. This heterodimer is composed of TCRy and TCRS polypeptides which are distinct from each other on the basis of immunochemical criteria (1-3) and by peptide mapping (4), and are encoded by different genes. The TCRy (5, 6) and TCRS (7-9) genes are composed of variable (V), joining (J), and constant (C) region segments that undergo somatic rearrangement in T cells (7, 10, 11), as is the case for TCRa, TCR a, and Ig genes. In the human germ-line, six or seven functional TCRy variable gene segments have been identified (12-14) that are located 5' of two constant region gene segments, designated Cyl and Cy2 (15). The TCRy constant gene segments consist of three exons, namely the CI exon (encoding an extracellular, Ig-like constant domain), a short CII exon (encoding a connecting peptide), and the CIII exon (encoding the membrane spanning can be accounted for by posttranslational processes on the PEER and IDP2 TCR-y glycoproteins (55-60 kD surface size minus 40-kD core size), only 5-11 kD of size on the mature MOLT-13 TCR-y glycoprotein is accounted for by posttranslational processes (40-46-kD surface size minus 35-kD core size). Experiments using tunicamycin to inhibit the addition of N-linked carbohydrates to the polypeptide chain confirmed that the posttranslational processing is largely, if not totally accounted for, by the addition of N-linked glycans (data not shown). Assuming that each glycan accounts for ti3 kD of relative molecular mass, we predict that two or three N-linked glycans are attached to the MOLT 13 TCR-y protein, while five N-linked glycans are added to the TCR-y polypeptides on PEER and IDP2 cells. of connector region that is the constant domain membrane spanning region. We show that the number ofpotential N-linked glycan sites are the for the two TCRy forms. Since these attachment sites are located in theconnector region we conclude that the connector region the amount ofN-linked carbohydrates addedto the core TCRy polypeptide, probably by affecting the conformation of the protein. In contrast to the TCR-R constant region usage, the TCRy constant regions are unequally Vir-tually exclusive usage of disulfide-linked in some individuals, both the disulfide-linked and the 40-kD, non-disulfide-linked TCR-y forms in other subjects. The to these TCR-y/8 forms now it possible to study the mechanisms that govern their selection and to determine if they correspond to functionally distinct isotypes.

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