Cutting Edge: The HLA-A0101-Restricted HY Minor Histocompatibility Antigen Originates from DFFRY and Contains a Cysteinylated Cysteine Residue as Identified by a Novel Mass Spectrometric Technique

• Published in: The Journal of immunology (1950) 1999-12, Vol.163 (12), p.6360-6364
• Main Authors: Pierce, Richard A, Field, Erin D, den Haan, Joke M. M, Caldwell, Jennifer A, White, Forest M, Marto, Jarrod A, Wang, Wei, Frost, Leslie M, Blokland, Els, Reinhardus, Carla, Shabanowitz, Jeffrey, Hunt, Donald F, Goulmy, Els, Engelhard, Victor H
• Format: Article
• Language: English
• Subjects: Antigens, Surface - isolation & purification; Antigens, Surface - metabolism; Cells, Cultured; Cysteine - metabolism; Disulfides - metabolism; Epitopes - isolation & purification; Female; H-Y Antigen - isolation & purification; H-Y Antigen - metabolism; HLA-A Antigens - immunology; Humans; Male; Mass Spectrometry - methods; Methionine - metabolism; X Chromosome - genetics; Y Chromosome - genetics
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.163.12.6360

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.