Journal of Experimental Medicine, Vol 158, 1573-1588, Copyright © 1983 by Rockefeller University Press

ARTICLES

Serologic and functional characterization of a panel of antigen- presenting cell lines expressing mutant I-A class II molecules

LH Glimcher, SO Sharrow and WE Paul

An improved method is described for selecting mutant cells with an altered pattern of Ia antigenic determinants and antigen-presenting properties from an homogeneous population of functional antigen- presenting cells (APC). The APC line used, TA3, was a somatic cell hybrid obtained by fusing normal heterozygous H-2a/d B cells with a drug-marked variant of a BALB/c B lymphoma line. Two phenotypic groups of mutants were obtained by this method. Serologic analysis with a panel of anti-I-Ak monoclonal antibodies suggested that the change in the first group of mutants (type A mutants) involved the alteration of a portion of one epitope of the I-Ak molecule while in the second group of mutants (type B), an alteration of a different Ia epitope group had occurred. Functional studies using a panel of cloned antigen-specific and autoreactive T cell hybridomas demonstrated that the loss of a limited number of I-Ak determinants in the type A mutants correlated with the loss of some but not all I-Ak-encoded restriction elements, while the type B mutation(s) resulted in the ablation of all I-Ak- restricted APC functions tested. These mutations may occur in the region of the Ia molecule that interacts with the T cell receptor (the histope) or in a postulated region that interacts with antigen (the desetope). The finding that both type A and B mutations lead to loss in the capacity to be corecognized with many different antigens by I-Ak- restricted T cell hybridomas suggests that the Ia molecule may possess very few distinct histotopes and/or desetopes or that the tertiary structure of the Ia molecule is crucial in the formation of these sites. Alternatively, the mutations, particularly the type B mutations, may have led to the failure of expression of an entire alpha or beta chain.
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This article has been cited by other articles:

• Yang, L., Kobie, J. J., Mosmann, T. R. (2005). CD73 and Ly-6A/E Distinguish In Vivo Primed but Uncommitted Mouse CD4 T Cells from Type 1 or Type 2 Effector Cells. J. Immunol. 175: 6458-6464 [Abstract] [Full Text]  
• Brown, M., Glimcher, L., Nielsen, E., Paul, W., Germain, R. (1986). T-cell recognition of Ia molecules selectively altered by a single amino acid substitution. Science 231: 255-258 [Abstract]  

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