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 instrumentat ion to identify a male-specific minor histocompatibility Ag restricted by H LA-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 hy the substitution of serine for the C* residue. Both peptides are expressed on the cell surf ace at 30 or fewer copies per cell. However, Al-HY-specific CTL recognize t he DFFRY-derived peptide at a 1500-fold lower dose than the female homologu e, Thus, these studies have identified a new source of HY epitopes and prov ide additional information about the influence of posttranslational modific ations of class I-associated peptides on T cell recognition.