Conformational and biochemical differences in the TCR.CD3 complex of CD8(+) versus CD4(+) mature lymphocytes revealed in the absence of CD3gamma.
Mature CD4(+) and CD8(+) T lymphocytes are believed to build and express essentially identical surface alphabeta T-cell receptor-CD3 (TCR.CD3) complexes. However, TCR.CD3 expression has been shown to be more impaired in CD8(+) cells than in CD4(+) cells when CD3gamma is absent in humans or mice. We have addressed this paradox by performing a detailed phenotypical and biochemical analysis of the TCR.CD3 complex in human CD3gamma-deficient CD8(+) and CD4(+) T cells. The results indicated that the membrane TCR.CD3 complex of CD8(+) T lymphocytes was conformationally different from that of CD4(+) lymphocytes in the absence of CD3gamma. In addition, CD8(+), but not CD4(+), CD3gamma-deficient T lymphocytes were shown to contain abnormally glycosylated TCRbeta proteins, together with a smaller, abnormal TCR chain (probably incompletely processed TCRalpha). These results suggest the existence of hitherto unrecognized biochemical differences between mature CD4(+) and CD8(+) T lymphocytes in the intracellular control of alphabetaTCR. CD3 assembly, maturation, or transport that are revealed when CD3gamma is absent. Such lineage-specific differences may be important in receptor-coreceptor interactions during antigen recognition.
Zapata
D A
DA
Inmunología, Facultad de Medicina, Universidad Complutense, 28040 Madrid, Spain.
Pacheco-Castro
A
A
Torres
P S
PS
Ramiro
A R
AR
San José
E
E
Alarcón
B
B
Alibaud
L
L
Rubin
B
B
Toribio
M L
ML
Regueiro
J R
JR
D015152:Blotting, Northern; D017252:CD3 Complex / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D005434:Flow Cytometry; D019673:Genes, T-Cell Receptor alpha / Q000235:genetics; D006567:Herpesvirus 2, Saimiriine / Q000276:immunology; D006801:Humans; D010641:Phenotype; D011233:Precipitin Tests; D011487:Protein Conformation; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000737:chemistry* / Q000235:genetics; D011956:Receptors, Cell Surface / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic
D017252:CD3 Complex; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011956:Receptors, Cell Surface; D002118:Calcium