Cutting edge: the HLA-A*0101-restricted HY minor histocompatibility antigen originates from DFFRY and contains a cysteinylated cysteine residue as identified by a novel mass spectrometric technique.
In this report, we describe the use of novel mass spectrometry instrumentation to identify a male-specific minor histocompatibility Ag restricted by HLA-A*0101 (A1-HY). This Ag has the sequence IVDC*LTEMY, where C* represents a cysteine disulfide bonded to a second cysteine residue. The core peptide sequence is found in the protein product of DFFRY, a Y chromosome gene not previously identified as the source of an HY Ag. The male-specific form of the peptide differs from its X chromosomal counterpart by the substitution of serine for the C* residue. Both peptides are expressed on the cell surface at 30 or fewer copies per cell. However, A1-HY-specific CTL recognize the DFFRY-derived peptide at a 1500-fold lower dose than the female homologue. Thus, these studies have identified a new source of HY epitopes and provide additional information about the influence of posttranslational modifications of class I-associated peptides on T cell recognition.
Pierce
R A
RA
Department of Microbiology, Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville 22908, USA.
Field
E D
ED
den Haan
J M
JM
Caldwell
J A
JA
White
F M
FM
Marto
J A
JA
Wang
W
W
Frost
L M
LM
Blokland
E
E
Reinhardus
C
C
Shabanowitz
J
J
Hunt
D F
DF
Goulmy
E
E
Engelhard
V H
VH
D000954:Antigens, Surface / Q000302:isolation & purification / Q000378:metabolism; D002478:Cells, Cultured; D003545:Cysteine / Q000378:metabolism*; D004220:Disulfides / Q000378:metabolism; D000939:Epitopes / Q000302:isolation & purification; D005260:Female; D006182:H-Y Antigen / Q000302:isolation & purification / Q000378:metabolism*; D015234:HLA-A Antigens / Q000276:immunology*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008715:Methionine / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics; D014998:Y Chromosome / Q000235:genetics
D000954:Antigens, Surface; D004220:Disulfides; D000939:Epitopes; D006182:H-Y Antigen; D015234:HLA-A Antigens; D008715:Methionine; D003545:Cysteine