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Cell-surface expression of human histocompatibility leucocyte antigen (HLA) class II-associated invariant chain
K M Wilson1, M O Labeta, G Pawelec
1Department of Biology, University of Essex, Colchester, U.K.
Insights
CD74, a component of human leukocyte antigen (HLA) class II, is expressed on all B cells. Unexpectedly, CD74 is not synthesized on de novo-induced class II positive T cells, despite their expression of class II determinants.
Area of Science:
- Immunology
- Cell Biology
Background:
- The human histocompatibility leucocyte antigen (HLA) class II-associated invariant chain includes at least four polypeptides, one designated CD74, expressed as a membrane-bound subunit.
- Understanding CD74 expression is crucial for deciphering immune cell function and regulation.
Purpose of the Study:
- To investigate the expression patterns of CD74 on human B and T cell types.
- To determine the relationship between HLA class II expression and CD74 synthesis in different immune cell populations.
Main Methods:
- Utilized monoclonal antibodies (mAb) specific for the c-terminus of CD74 to detect its expression.
- Analyzed CD74 expression on various B cell types and T cell lines, including those with selective or total class II deletions.
- Examined CD74 expression on peripheral blood T cells and allostimulated T cells.
Main Results:
- All tested B cells expressed CD74, with quantitative variations observed in some haplotypes.
- A mutant cell with partial class II deletion synthesized normal CD74 amounts, while total class II deletion diminished CD74 expression.
- Major histocompatibility complex (MHC) class II negative T-cell lines and peripheral blood T cells did not express CD74.
- Allostimulated T cells, despite de novo induced class II determinants, also failed to express CD74.
Conclusions:
- CD74 is constitutively expressed on all B cells, with its full expression potentially dependent on at least one MHC class II isotype.
- Contrary to expectations, CD74 is not synthesized by de novo-induced class II positive T-cell clones, highlighting a distinct regulatory mechanism in T cells.
Abstract:
The human histocompatibility leucocyte antigen (HLA) class II-associated invariant chain comprises at least four polypeptides. One of these is expressed as a membrane-bound subunit and has been designated as CD74. We investigated the expression of CD74 on B- and T-cell types utilizing monoclonal antibodies (mAb) specific for the c-terminus of CD74. All B cells tested expressed CD74 regardless of their HLA phenotypes. High and low CD74 expressors were provisionally assigned based on quantitative variations found in some haplotypes. A mutant cell with selective deletions of class II loci DR and DQ but with retention of DP and additional class II heterodimers synthesize normal amounts of CD74. In contrast, however, a mutant with a total class II deletion had diminished expression of CD74, suggesting that at least one of the class II isotypes is essential for full constitutive expression of CD74. Major histocompatibility complex (MHC) class II negative T-cell lines and CD3+ T cell isolated from peripheral blood did not express CD74. However, allostimulated T cells which express de novo induced class II determinants also did not express CD74. Taken together, these results show that CD74 is expressed on B cells and unexpectedly is not synthesized on de novo-induced class II positive T-cell clones.
