Marked differences in the efficiency of expression of distinct alpha beta T cell receptor heterodimers.
Ag recognition by most T lymphocytes is mediated by clonally distributed alpha beta heterodimeric receptors. A major fraction of TCR diversity is believed to be due to the random coexpression in individual T cells of the products of independently rearranging alpha- and beta-genes (combinatorial diversity). However, analysis of cell surface receptors on transfected T hybridoma cells synthesizing various sets of alpha- and beta-chains revealed marked differences in the efficiency of expression of certain alpha beta-pairs. Specifically, using the functionally rearranged gene products of the 2B4 cytochrome c specific T hybridoma (V beta 3, V alpha 11.2) and BW5147 parent lymphoma (V beta 1, V alpha BW), a hierarchy of expression efficiency relative to indirectly measured precursor chain levels in the cell was shown to be 2B4 alpha-BW beta greater than 2B4 alpha - 2B4 beta greater than BW alpha - BW beta greater than BW alpha - 2B4 beta. The estimated difference between the best expressed and worst expressed pairs is on the order of 50-fold. For the beta-chain, the primary determinant of expression efficiency with a given alpha-chain appears to be the V segment, as a second V beta 1-chain with distinct D and J regions from BW beta was expressed with the same pattern. These data imply that alpha- and beta-chains do not form well-expressed TCR in a random manner and that limitations on the useful combinatorial association of these chains may significantly affect the functional T cell repertoire.
Saito
T
T
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Sussman
J L
JL
Ashwell
J D
JD
Germain
R N
RN
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D005796:Genes; D051379:Mice; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012333:RNA, Messenger / Q000302:isolation & purification; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000378:metabolism*; D014162:Transfection
D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell