The A′ and F′ pockets of human CD1b are both required for optimal presentation of lipid antigens to T cells

K. R. Niazi, M. W. Chiu, R. M. Mendoza, M. Degano, S. Khurana, D. B. Moody, A. Melián, I. A. Wilson, M. Kronenberg, S. A. Porcelli, R. L. Modlin

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

CD1 proteins are unique in their ability to present lipid Ags to T cells. Human CD1b shares significant amino acid homology with mouse CD1d1, which contains an unusual putative Ag-binding groove formed by two large hydrophobic pockets, A′ and F′. We investigated the function of the amino acid residues that line the A′ and F′ pockets of CD1b by engineering 36 alanine-substitution mutants and analyzing their ability to present mycobacterial glycolipid Ags. Two lipid Ags presented by CD1b were studied, a naturally occurring glucose monomycolate (GMM) isolated from mycobacteria, which contains two long alkyl chains (C54-C62 and C22-C24) and synthetic GMM (sGMM), which includes two short alkyl chains (C18 and C14). We identified eight residues in both the A′ and F′ pockets that were involved in the presentation of both GMM and sGMM to T cells. Interestingly, four additional residues located in the distal portion of the A′ pocket were required for the optimal presentation of GMM, but not sGMM. Conversely, nine residues located between the center of the groove and the F′ pocket were necessary for the optimal presentation of sGMM, but not GMM. These data indicate that both the A′ and F′ pockets of human CD1b are required for the presentation of lipid Ags to T cells.

Original languageEnglish
Pages (from-to)2562-2570
Number of pages9
JournalJournal of Immunology
Volume166
Issue number4
Publication statusPublished - Feb 15 2001

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Antigen Presentation
T-Lymphocytes
Lipids
Amino Acids
Glycolipids
Mycobacterium
Alanine
glucose mycolate
Gm(m)
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Niazi, K. R., Chiu, M. W., Mendoza, R. M., Degano, M., Khurana, S., Moody, D. B., ... Modlin, R. L. (2001). The A′ and F′ pockets of human CD1b are both required for optimal presentation of lipid antigens to T cells. Journal of Immunology, 166(4), 2562-2570.

The A′ and F′ pockets of human CD1b are both required for optimal presentation of lipid antigens to T cells. / Niazi, K. R.; Chiu, M. W.; Mendoza, R. M.; Degano, M.; Khurana, S.; Moody, D. B.; Melián, A.; Wilson, I. A.; Kronenberg, M.; Porcelli, S. A.; Modlin, R. L.

In: Journal of Immunology, Vol. 166, No. 4, 15.02.2001, p. 2562-2570.

Research output: Contribution to journalArticle

Niazi, KR, Chiu, MW, Mendoza, RM, Degano, M, Khurana, S, Moody, DB, Melián, A, Wilson, IA, Kronenberg, M, Porcelli, SA & Modlin, RL 2001, 'The A′ and F′ pockets of human CD1b are both required for optimal presentation of lipid antigens to T cells', Journal of Immunology, vol. 166, no. 4, pp. 2562-2570.
Niazi, K. R. ; Chiu, M. W. ; Mendoza, R. M. ; Degano, M. ; Khurana, S. ; Moody, D. B. ; Melián, A. ; Wilson, I. A. ; Kronenberg, M. ; Porcelli, S. A. ; Modlin, R. L. / The A′ and F′ pockets of human CD1b are both required for optimal presentation of lipid antigens to T cells. In: Journal of Immunology. 2001 ; Vol. 166, No. 4. pp. 2562-2570.
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