Characteristics of the camelidae (camel, llama) antibody synthesis

The Arabian camel (Camelus dromedarius) and the llama (Lama glama) have three IgG subclasses: the conventional IgG1 and the non-conventional IgG2 and IgG3.

IgG2 and IgG3 are characterized by the absence of light chain. This lack of light chain is itself a consequence of the absence of the CH1 domain in the gamma 2 and gamma 3 chains, due to a splicing defect of the CH1 exon (non canonical DONOR-SPLICE: nat instead of ngt) (Gene table: IGHC camel).

This situation is similar to that found in human in Heavy Chain Diseases (HCDs)

The camelidae IGHV genes (Gene table: IGHV camel, IGHV llama, Protein display: IGHV camel, IGHV llama) belong to the IGHV1 subgroup and comprise two sets, the first set (IGHV1S1 to IGHV1S41) observed in the gamma 1 chains of the conventional IgG1 and the second set (IGHV1S42 to IGHV1S74) observed in the gamma 2 and gamma 3 chains of the non conventional IgG2 and IgG3.

The Camelidae IGHV genes of second set genes (IGHV1S42 to IGHV1S74) show four amino acid changes at positions 42 (F, Y), 49 (E, Q), 50 (C, R) and 52 (F, G, L, W) according to the IMGT unique numbering, which make the C' strand more hydrophilic (IMGT Colliers de Perles, IGHV1S45). This co-evolution of the variable region (more hydrophilic) and of the constant region (absence of CH1 due to a mutation in the splicing site) is particularly remarkable.

Interestingly, the CDR3-IMGT of the VH domains (V-D-J-REGION) that involve V genes of the second set is longer than the average length of 13 amino acids, usually observed for conventional antibodies. As the antibody specificity is confered by a single domain, these VH domains also referred as VHH domains are frequently used in antibody engineering.