A subset of HLA-B27 molecules contains peptides much longer than nonamers

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Item Type:	Article
Title:	A subset of HLA-B27 molecules contains peptides much longer than nonamers
Creators Name:	Urban, R.G., Chicz, R.M., Lane, W.S., Strominger, J.L., Rehm, A., Kenter, M.J., UytdeHaag, F.G., Ploegh, H., Uchanska-Ziegler, B. and Ziegler, A.
Abstract:	An unusual monoclonal antibody (MARB4) directed against HLA-B27 that reacts with only approximately 5-20% of the cell surface HLA-B27 was used for large-scale purification of these molecules. Subsequent mass spectrometry of HLA-B27-bound peptides showed that the minor MARB4-reactive population contained peptides primarily from 900 to 4000 Da in size (approximately 8-33 amino acid residues), whereas the major HLA-B27 population contained peptides in the mass range of 900-1400 Da (approximately 8-12 amino acid residues). Thus, a subset of HLA-B27 molecules binds to peptides much longer than nonamers. Typical HLA-B27-binding peptides contain arginine in position 2. Further analysis by Edman sequencing of the pooled bound peptides revealed that the major population contained substantial amounts of arginine at positions 1 and 9 (40-50%) and exclusively arginine at position 2, as expected. The minor population of peptides also contained detectable amounts of arginine at these positions, but at the level of only approximately 10%; no marked enrichment at any position was observed. These long HLA-B27-bound peptides could represent either intermediates in the formation of nonamers or adventitiously bound peptides. Lastly, in the TAP2 mutant cell line BM36.1 transfected with HLA-B*2705, MARB4-reactive HLA-B27 molecules were absent from the cell surface, indicating that the peptide transporter was required for delivery of the long peptides. Thus, during the folding of class I heavy chains, peptides of diverse lengths are available and participating.
Keywords:	ATP-Binding Cassette Transporters, Amino Acid Sequence, B-Lymphocytes, Carrier Proteins, HLA-B27 Antigen, Histocompatibility Antigens Class II, Member 3 Subfamily B ATP Binding Cassette Transporter, Molecular Sequence Data, Monoclonal Antibodies, Peptides, Protein Binding, Sequence Analysis, Transfection, Transformed Cell Line, Viral Cell Transformation
Source:	Proceedings of the National Academy of Sciences of the United States of America
ISSN:	0027-8424
Publisher:	National Academy of Sciences
Volume:	91
Number:	4
Page Range:	1534-1538
Date:	15 February 1994
Additional Information:	Copyright © National Academy of Sciences.
Official Publication:	https://doi.org/10.1073/pnas.91.4.1534
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