The TAP complex influences allorecognition of class II MHC molecules.
The influence of the TAP complex on T-cell allorecognition of MHC class II molecules was examined using human B-cell lines that have mutations in the TAP 1 or 2 genes. The TAP mutations led to the loss of allorecognition for two of 28 anti- HLA-DR T-cell clones. Restoration of TAP expression by transfection of a TAP 2 cDNA clone led to recovery of the alloresponse for both clones. These results could be explained in two ways. First, TAP dependence could reflect specificity for a peptide derived from an MHC class I molecule that is less efficiently generated by the endocytic pathway in the TAP-deficient stimulator cells owing to reduction in surface class I expression. The proliferative responses of these clones to the TAP-deficient stimulator cells was not restored by rescue of cell-surface expression of class I molecules by low temperature culture or by the addition of class I-binding peptides. These data therefore favor the alternative explanation that class II loading by some peptides is TAP dependent. Circumstances that lead to the amplification of this minority pathway of endogenous presentation by class II MHC molecules may have the potential to interrupt self-tolerance.
Carmichael
P
P
Department of Immunology, Royal Postgraduate Medical School, London, United Kingdom.
Kerr
L A
LA
Kelly
A
A
Lombardi
G
G
Zeigler
B U
BU
Ziegler
A
A
Trowsdale
J
J
Lechler
R
R
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000032:analysis* / Q000276:immunology*; D017951:Antigen Presentation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D006681:HLA-D Antigens / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D006681:HLA-D Antigens; D007519:Isoantigens; C073119:TAP1 protein, human; C071692:TAP2 protein, human