Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9264498 | Human Immunology | 2005 | 9 Pages |
Abstract
A new variant of the HLA-A*010101 allele designated as HLA-A*0111N, previously known as HLA-A*010101var, was identified in a patient requiring a stem-cell transplantation. The patient was typed by serologic methods as HLA-A2 homozygous and by sequence-based typing (SBT) as A*010101,020601. Flow-cytometric (FCM) analysis with 11 human monoclonal antibodies (mAbs) for the A1 molecule confirmed lack of any cell membrane expression of the A*0111N allele. One-dimensional isoelectric focusing (1D-IEF) of total cell lysate from the patient's cells revealed no cell surface and cytoplasmic A1 protein expression, whereas the HLA-A2 molecule was identified by both FCM analysis and 1D-IEF. DNA sequence analysis showed the presence of a synonymous substitution from G to T at position 597 in codon 175. RNA SBT revealed a deletion of 24 bp in exon 3, position 596 through 619, encoding codons 175 through 182 of the HLA-A*0111N allele. The synonymous substitution introduced a new splice site, resulting in an efficient splicing, because no classical A1 protein could be detected in the patient. This alternative splicing prevented the translation into a correct and stable class I molecule expression on the cell surface.
Keywords
1D-IEFFCMmAbUTRGAPDHSBTScTNull alleleMonoclonal antibodyHuman leukocyte antigenHLAMatched unrelated donorEBVsequence-based typingone-dimensional isoelectric focusingAlternative splicinguntranslated regionpolymerase chain reactionPCREpstein-Barr virusStem-cell transplantationMudglyceraldehyde-3-phosphate dehydrogenase
Related Topics
Life Sciences
Immunology and Microbiology
Immunology
Authors
Judith Reinders, Erik H. Rozemuller, Henny G. Otten, Anna J.S. Houben, Anne Dormoy, Arend Mulder, Jan G. van den Tweel, Eefke J. Petersen, Marcel G.J. Tilanus,