Abstract
Research addressing the in vivo effects of T cell activation by lipids, glycolipids, and lipopeptides is hampered by the absence of a suitable animal model. Mice and rats do not express CD1a, CD1b, and CD1c molecules that present pathogen-derived lipid antigens in humans. In cattle, two CD1A and three CD1B genes are transcribed. The proteins encoded by these genes differ in their antigen binding domains and in their cytoplasmic tails, suggesting that they may traffic differently in the cell and thus have access to different antigens. In the current study, we describe the genomic organization of the bovine CD1 locus and transcription of bovine CD1 genes in freshly isolated dendritic cells and B cells from different tissues. After determining the specificity of previously only partly characterized anti-CD1 antibodies by testing recombinant single chain bovine CD1 proteins and CD1-transfected cells, we were able to determine cell surface protein expression on freshly isolated cells. Our study suggests that CD1b1 and CD1b3 are more broadly expressed than CD1b5, and CD1a2 is more broadly expressed than CD1a1. Pseudoafferent lymph dendritic cells express CD1B genes, but no transcription is detected in lymph nodes. Even though B cells transcribe CD1B genes, there is no evidence of protein expression at the cell surface. Thus, patterns of CD1 protein expression are largely conserved among species.
Highlights
And structurally, the CD1 family of proteins can be divided in two groups
We have previously shown that bovine group 2 CD1 (CD1d) is expressed, but does not seem to fulfill the model function of presenting α-galactosylceramide to NKT cells and cause the release of cytokines [13]
One question we had is whether group 1 and group 2 CD1 molecules, even when the numbers of genes, and possibly their functions are different, follow the typical group 1 and group 2 CD1 expression patterns in the sense that group 1 CD1 is present on thymocytes and dendritic cells, and not on non-hematopoietic cells, while group 2 CD1 has a broader expression pattern and includes B cells and non-hematopoietic cells
Summary
And structurally, the CD1 family of proteins can be divided in two groups. Genes for group 1 CD1 proteins (CD1a, CD1b, and CD1c) are lacking in mice, but in humans, group. Group 1 CD1 proteins are best known for their ability to present bacterial lipid antigens to T cells, though CD1a has been shown to be recognized by T cells without the addition of foreign antigen [3, 4]. Dogs have eight CD1A genes [5], guinea pigs have five CD1B genes and four CD1C genes [6], and humans have one gene for each isoform. Most of the known group 1 CD1-presented antigens are from mycobacterial origin, including M. tuberculosis and M. leprae, which cause human tuberculosis and leprosy, and M. bovis, which causes bovine tuberculosis. Identification of functional orthologs of CD1 molecules is relevant to the development and testing of experimental vaccines that incorporate lipid antigens
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