Abstract
The adaptive immune receptors repertoire is highly plastic, with its ability to produce antigen-binding molecules and select those with high affinity for their antigen. Species have developed diverse genetic and structural strategies to create their respective repertoires required for their survival in the different environments. Camelids, until now, considered as a case of evolutionary innovation because of their only heavy-chain antibodies, represent a new mammalian model particularly useful for understanding the role of diversity in the immune system function. Here, we review the structural and functional characteristics and the current status of the genomic organization of camel immunoglobulins (IG) or antibodies, α/ß and γ/δ T cell receptors (TR), and major histocompatibility complex (MHC). In camelid humoral response, in addition to the conventional antibodies, there are IG with “only-heavy-chain” (no light chain, and two identical heavy gamma chains lacking CH1 and with a VH domain designated as VHH). The unique features of these VHH offer advantages in biotechnology and for clinical applications. The TRG and TRD rearranged variable domains of Camelus dromedarius (Arabian camel) display somatic hypermutation (SHM), increasing the intrinsic structural stability in the γ/δ heterodimer and influencing the affinity maturation to a given antigen similar to immunoglobulin genes. The SHM increases the dromedary γ/δ repertoire diversity. In Camelus genus, the general structural organization of the TRB locus is similar to that of the other artiodactyl species, with a pool of TRBV genes positioned at the 5’ end of three in tandem D-J-C clusters, followed by a single TRBV gene with an inverted transcriptional orientation located at the 3’ end. At the difference of TRG and TRD, the diversity of the TRB variable domains is not shaped by SHM and depends from the classical combinatorial and junctional diversity. The MHC locus is located on chromosome 20 in Camelus dromedarius. Cytogenetic and comparative whole genome analyses revealed the order of the three major regions “Centromere-ClassII-ClassIII-ClassI”. Unexpectedly low extent of polymorphisms and haplotypes was observed in all Old World camels despite different geographic origins.
Highlights
In vertebrates, B and T lymphocytes together with the antigenpresenting cells play central roles in the adaptive immune system
They respond to a large variety of antigens that are recognized through highly specialized proteins: immunoglobulins (IG) or antibodies in B cells, and T cell receptors (TR) in T cells (Lefranc, 2014a)
In contrast in the TR alpha/beta, only the two CDR3 principally recognize and bind the antigenic peptide bound to major histocompatibility (MH) proteins of class I (MH1) or class II (MH2), whereas the germline-encoded CDR1 and CDR2 loops mainly contact the helices of the MH proteins (Lefranc, 2014a)
Summary
B and T lymphocytes together with the antigenpresenting cells play central roles in the adaptive immune system. IGHV genes encoding VH and VHH domains as well as the IGHG genes encoding the C-REGION of conventional IG (IGHG1) and only-heavy-chain IG (IGHG2 and IGHG3) are in an intermixed conformation, in V and C clusters, respectively, in a single IGH locus (Figure 1).
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