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The Journal of Immunology, 2003, 171: 3.
Copyright © 2003 by The American Association of Immunologists

MHC Class I Peptide Binding and Tapasin

Carlos Vilches

Servicio de Inmunología, Hospital Universitario Puerta de Hierro, Madrid, Spain

Park et al. (1) have recently proposed that the variable tapasin-dependence in the expression of HLA class I molecules is controlled by polymorphisms of residue 114 of the {alpha}-chain, the highest dependence being conferred by acidic residues. Their findings conflict with those published by Williams et al. (2), who found B*4405, an allele bearing aspartic acid in residue 114, to be expressed independently of tapasin. Park et al. question this result, based on flow cytometry studies, reasoning that B*4405 is devoid of {alpha}3, transmembrane and cytoplasmic domains and should be rather a soluble than a membrane-associated protein (1). However, these affirmations are based on a misinterpretation of the B*4405 nucleotide sequence reported by Petersdorf et al. (3). The sequencing strategy used in the referenced study enabled the authors to characterize only the exons encoding the {alpha}1 and {alpha}2 domains of B*4405, which does not mean that this allele lacks all other exons, as concluded by Park et al. Furthermore, we have determined the cDNA sequence of B*4405 (EMBL AJ535113, unpublished), of which the coding region is identical to that of B*4402 (a tapasin-dependent allele), except for the already known change that determines substitution of tyrosine for aspartate 116. Therefore, the natural allele B*4405 and the tapasin-dependent mutant B44D116Y generated from B*4402 by Park et al. (1) should have indistinguishable structures and functions, and the discrepant results and conclusions obtained with each of those molecules (1, 2) can only be attributed to methodological differences between the two studies.


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  1. Park, B., S. Lee, E. Kim, K Ahn. 2003. A single polymorphic residue within the peptide-binding cleft of MHC class I molecules determines spectrum of tapasin dependence. J. Immunol. 170:961.[Abstract/Free Full Text]
  2. Williams, A. P., C. A. Peh, A. W. Purcell, J. McCluskey, T. Elliott. 2002. Optimization of the MHC class I peptide cargo is dependent on tapasin. Immunity 16:509.[Medline]
  3. Petersdorf, E. W., T. Setoda, A. G. Smith, J. A. Hansen. 1994. Analysis of HLA-B*44 alleles encoded on extended HLA haplotypes by direct automated sequencing. Tissue Antigens 44:211.[Medline]



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