Human peptide transporter deficiency: importance of HLA-B in the presentation of TAP-independent EBV antigens.
Two siblings with a peptide TAP deficiency were recently described. Despite poor cell surface expression of HLA class I molecules, these patients were not unusually susceptible to viral infections. The majority of the cell surface-expressed class I molecules were HLA-B products as assessed by cytofluorometry and biochemical analysis. Analysis of two peptides eluted from the class I molecules expressed by TAP-deficient EBV B lymphoblastoid cell lines indicated that both were derived from cytosolic proteins and presented by HLA-B molecules. Peripheral alphabeta CD8+ T cells were present and their TCR repertoire was polyclonal. Most of the alphabeta CD8+ T cell clones studied (21 of 22) were nonreactive against cells expressing normal levels of the same HLA alleles as those of the TAP-deficient patients. However, it was possible to isolate one cytotoxic CD8+ alphabeta T cell clone recognizing the EBV protein LMP2 presented by HLA-B molecules on TAP-deficient cells. These observations suggest that in the TAP-deficient patients, CD8+ alphabeta T cells could mature and be recruited in immune responses to mediate HLA class I-restricted cytotoxic defense against viral infections. They also strengthen the physiologic importance of a TAP-independent processing pathway of the LMP2 protein, which was previously shown to contain several other TAP-independent epitopes.
de la Salle
H
H
Histocompatibility Laboratory, Contract for Young Research Unit INSERM 94-03 and INSERM Unit 311, Blood Transfusion Establishment, Strasbourg, France.
Houssaint
E
E
Peyrat
M A
MA
Arnold
D
D
Salamero
J
J
Pinczon
D
D
Stevanovic
S
S
Bausinger
H
H
Fricker
D
D
Gomard
E
E
Biddison
W
W
Lehner
P
P
UytdeHaag
F
F
Sasportes
M
M
Donato
L
L
Rammensee
H G
HG
Cazenave
J P
JP
Hanau
D
D
Tongio
M M
MM
Bonneville
M
M
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D015235:HLA-B Antigens / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D010455:Peptides / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000956:Antigens, Viral; D015235:HLA-B Antigens; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; C071692:TAP2 protein, human