The Q7 α3 domain alters T cell recognition of class I antigens

Carla Aldrich, L. C. Lowen, D. Mann, M. Nishimura, L. Hood, I. Stroynowski, J. Forman

Research output: Contribution to journalArticle

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Abstract

In this study we have analyzed the role of the α3 domain of class I molecules in T cell recognition. Using the laboratory engineered molecules LLQQ (α1/α2 from Ld, α3, and phosphatidyl inositol (PI) linked C terminus from Q7) and LLQL (α1/α2 from Ld, α3 from Q7, transmembrane (TM) and cytoplasmic domains from Ld) we show that these molecules are not recognized by primary Ld-specific CTL. The cell membrane expression of both Ld and LLQL are upregulated by co-culture with an exogenously supplied murine cytomegalovirus-derived peptide indicating that the Q7 α3 domain does not interfere with binding of Ag to α1/α2. However, only peptide pulsed Ld but not LLQL target cells are recognized by Ld-restricted-peptide specific CTL. In contrast to the above results, LLQL and LLQQ molecules can be recognized by bulk alloreactive anti-Ld CTL and 2/3 of CTL clones derived from in vivo primed mice. The fact that these secondary CTL recognize LLQQ indicates that a PI linkage is permissive for presentation of class I epitopes to alloreactive CTL. These secondary CTL are resistant to blocking at the effector stage by mAb against CD8 and express relatively low levels of membrane CD8 molecules compared to CTL from unprimed mice. Further, culture of unprimed CTL precursors in the presence of CD8 mAb also allows for the generation of CD8-independent CTL that recognize LLQL. Taken together, these data indicate that the α3 domain of Q7 (Qa-2) prevents CD8-dependent CTL from recognizing Ld, regardless of whether the class I molecule is attached to the cell surface by a PI moiety or as a membrane spanning protein domain. We hypothesize that this defect in recognition is most likely due to an inability of CD8 to interact efficiently with the Q7 α3 domain and could account for why Q7 molecules do not serve as restricting elements for virus and minor H-Ag-specific CTL.

Original languageEnglish (US)
Pages (from-to)3082-3090
Number of pages9
JournalJournal of Immunology
Volume146
Issue number9
StatePublished - May 1 1991
Externally publishedYes

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Histocompatibility Antigens Class I
Phosphatidylinositols
T-Lymphocytes
Peptides
Muromegalovirus
Coculture Techniques
Epitopes
Membrane Proteins
Clone Cells
Cell Membrane
Viruses
Membranes

ASJC Scopus subject areas

  • Immunology

Cite this

Aldrich, C., Lowen, L. C., Mann, D., Nishimura, M., Hood, L., Stroynowski, I., & Forman, J. (1991). The Q7 α3 domain alters T cell recognition of class I antigens. Journal of Immunology, 146(9), 3082-3090.

The Q7 α3 domain alters T cell recognition of class I antigens. / Aldrich, Carla; Lowen, L. C.; Mann, D.; Nishimura, M.; Hood, L.; Stroynowski, I.; Forman, J.

In: Journal of Immunology, Vol. 146, No. 9, 01.05.1991, p. 3082-3090.

Research output: Contribution to journalArticle

Aldrich, C, Lowen, LC, Mann, D, Nishimura, M, Hood, L, Stroynowski, I & Forman, J 1991, 'The Q7 α3 domain alters T cell recognition of class I antigens', Journal of Immunology, vol. 146, no. 9, pp. 3082-3090.
Aldrich C, Lowen LC, Mann D, Nishimura M, Hood L, Stroynowski I et al. The Q7 α3 domain alters T cell recognition of class I antigens. Journal of Immunology. 1991 May 1;146(9):3082-3090.
Aldrich, Carla ; Lowen, L. C. ; Mann, D. ; Nishimura, M. ; Hood, L. ; Stroynowski, I. ; Forman, J. / The Q7 α3 domain alters T cell recognition of class I antigens. In: Journal of Immunology. 1991 ; Vol. 146, No. 9. pp. 3082-3090.
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