TY - JOUR
T1 - Amino acid residues distinct from the determinant region can profoundly affect activation of T cell clones by related antigens
AU - Shastri, N.
AU - Miller, A.
AU - Sercarz, E. E.
PY - 1986
Y1 - 1986
N2 - Hen egg-white lysozyme (HEL)-specific T cell clones derived from the C57BL/6 strain were found to be about 100-fold more sensitive to the closely related ring-necked pheasant lysozyme (REL) in a dose-dependent proliferation assay. This apparent heteroclicity of REL was independent of the fine specificity of the clones. However, when stimulations by corresponding cyanogen bromide-cleaved peptides (L2H and L2R) known to contain the determinants recognized by all of the clones were compared, the preference for REL was lost. Conversely, an HEL-specific, I-A(d)-restricted clone that did not respond to REL responded equally well to L2H and to L2R. Because the HEL/REL reactivity differences involved only the T cells and antigen-presenting cells (APC), and were correlated with differential sensitivity to the lysosomotropic drug chloroquine, it appears that the reactivity differences relate to the manner in which lysozymes are processed by the APC. Thus, conclusions about T cell 'clonal specificity', usually attributed to differences in recognition of the determinant regions, may in some cases reflect differential antigen handling that depends on sites on the molecule distant from the determinant.
AB - Hen egg-white lysozyme (HEL)-specific T cell clones derived from the C57BL/6 strain were found to be about 100-fold more sensitive to the closely related ring-necked pheasant lysozyme (REL) in a dose-dependent proliferation assay. This apparent heteroclicity of REL was independent of the fine specificity of the clones. However, when stimulations by corresponding cyanogen bromide-cleaved peptides (L2H and L2R) known to contain the determinants recognized by all of the clones were compared, the preference for REL was lost. Conversely, an HEL-specific, I-A(d)-restricted clone that did not respond to REL responded equally well to L2H and to L2R. Because the HEL/REL reactivity differences involved only the T cells and antigen-presenting cells (APC), and were correlated with differential sensitivity to the lysosomotropic drug chloroquine, it appears that the reactivity differences relate to the manner in which lysozymes are processed by the APC. Thus, conclusions about T cell 'clonal specificity', usually attributed to differences in recognition of the determinant regions, may in some cases reflect differential antigen handling that depends on sites on the molecule distant from the determinant.
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M3 - Article
C2 - 2416804
AN - SCOPUS:0022658364
SN - 0022-1767
VL - 136
SP - 371
EP - 376
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -