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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.

Additional file 6: Figure S2. (B) Dot-plot of the goat TRBV cluster sequence against itself. Description: Enlargement of the wider red box in (A) showing the pattern of parallel lines due to the tandem duplicative events of the TRBV5 and TRBV6 genes. The arrows indicate long homology lines determined by a repetitive TRBV5-TRBV6 base unit.

Additional file 4: Figure S1. Description of the goat TRBV genes. The IMGT Protein display of the goat TRBV genes. The deduced amino acid sequences of the goat TRBV genes were manually aligned according to IMGT unique numbering for the V-REGION [33] to maximize homology. Only functional genes, ORF and in-frame pseudogenes are shown. All sequences exhibit the typical framework regions (FR) and complementarity determining regions (CDR) and the four amino acids (depicted and indicated in bold): cysteine 23 (1st-CYS) in FR1-IMGT, tryptophan 41 (CONSERVED-TRP) in FR2-IMGT, hydrophobic (here L and M) 89, and cysteine 104 (2nd-CYS) in FR3-IMGT, with the exception of TRBV6–20 and TRBV6–21 that lack the CONSERVED-TRP and the 2nd-CYS, respectively. Conversely, CDR-IMGT vary in amino acid composition and length. The description of the strands and loops and of the FR-IMGT and CDR-IMGT is according to the IMGT unique numbering for V-REGION [33]. The amino acid length of the CDR-IMGT AA is also indicated in square brackets. (B-D), nucleotide and deduced amino acid sequences of the TRBD, TRBJ and TRDC genes. The consensus sequence of the heptamer and nonamer is provided at the top of the figure and is underlined. The numbering adopted for the gene classification is reported on the left of each gene.

Additional file 17: Figure S7. J-RS sequence logos. Description: Recombination signal sequence logos of the heptamers and nonamers of the goat and sheep TRGJ genes generated using Weblogo [55] The height of letters indicates the relative frequency of each nucleotide at that position.

Additional file 9: Figure S3. (C) Description of the goat TRBC genes. The IMGT Protein display of the goat TRBC gene compared with the human, sheep, pig and dromedary Cβ proteins. The descriptions of the strands and loops were collected according to the IMGT unique numbering for the C-DOMAIN [54].

Additional file 2: Table S2. Description of the unrelated TRB genes in the Capra hircus chromosome 4 genome assembly (NCBI Reference Sequence CM_004565.1). The position of all genes and their classification and functionality are reported.

Additional file 7: Figure S3. (A) Description of the goat TRBD genes. The inferred amino acid sequence of the TRBD genes in the three coding frames are reported.

Additional file 8: Figure S3. (B) Description of the goat TRBJ genes. The donor splice site for each TRBJ is shown. The canonical FGXG amino acid motifs are underlined. The TRBJ1–3 and TRBJ2–7 ORF and TRB3–6 pseudogene are indicated in italics.

Description of the TRA/TRD genes in the sheep genome assembly. The position of all genes and their classification and functionality are reported. (ZIP 39.6 kb)

The NJ tree inferred from the sheep and human TRAV gene sequences. The evolutionary analysis was conducted in MEGA5 [36]. The percentage of replicate trees in which the associated taxa clustered together in the bootstrap test (1000 replicates) is shown next to the branches [40]. The trees are drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic trees. The evolutionary distances were computed using the p-distance method [37] and are in the units of the number of base differences per site. The sheep TRAV subgroup classification is according to the corresponding human TRAV subgroups. Sheep-specific subgroups are numbered from TRAV42 (boxed in the right column). The TRAV genes found in humans and not in sheep are boxed in the tree. The gene functionality according to IMGT rules (F: functional, ORF: open reading frame, P: pseudogene) is indicated. For each subgroup, the CDR1-IMGT, CDR2-IMGT and CDR3-IMGT lengths are reported between brackets in the right column: when different between species, the first is for the human subgroup and the second is for the sheep subgroup. For TRAV42 to TRAV45, the CDR-IMGT lengths are for the sheep subgroup only (no corresponding subgroup in humans). The IMGT 6-letter standardised abbreviation for taxon is used: three letters for genus and three letters for species (Homsap, Oviari). (PPT 7.56 kb)

TRA genes. In a, the IMGT Protein display of the sheep TRAV genes. Only functional genes ORF and in-frame pseudogenes are shown. The description of the strands and loops and of the FR-IMGT and CDR-IMGT is according to the IMGT unique numbering for V-REGION [27]. The CDR-IMGT AA lengths are indicated in square brackets. nd: not defined (indicates that the AA sequence of the TRAV45S1 gene is incomplete and its functionality cannot be defined). In b, nucleotide and deduced AA sequences of the sheep TRAJ genes. The numbering adopted for the gene classification is reported on the left of each gene. The functionality is also reported. The consensus sequences of the J-heptamer and J-nonamer [41] are provided at the top of the figure and underlined. The donor splice site for each TRAJ is also shown. The canonical F/W-G-X-G amino acid motifs are underlined. In c, IMGT Protein display of the TRAC gene. Description of the strands and loops is according to the IMGT unique numbering for C-DOMAIN [42]. (ZIP 325 kb)

Corrispondence between ovine and bovine germline TRAV repertoires. The bovine TRAV gene sequences were retrieved by Connelley et al. [16]. Correspondence was established as reported in Methods. (DOC 59 kb)

Analysis of the genomic structure of the sheep TRA/TRD locus. The sheep masked sequence was aligned versus itself and the alignment is showed as percentage identity plot (pip). The position and orientation of all genes are indicated, together with the location and orientation of the interspersed repeats as well. Horizontal lines represent ungapped alignments at the percentage identity corresponding to the scale on the right to the sequences. The presence in the pip of superimposed lines indicates the occurrence of redundant matches along the entire region. The clearest matches are in corresponding of all sheep variable genes due to the homology among genes. (PPT 570 kb)

Evolutionary relationship of the sheep TRDV genes. The TRDV nomenclature is according to IMGT-ONTOLOGY concepts of classification [28]. (PDF 7.56 kb)

Protein display of the TRA cDNA clones. The TRAV and TRAJ genes, named in accordance with the criteria specified in the text, are listed respectively at the left and the right of the figure. The cDNA clones are grouped by TRAV subgroups and those containing the same TRAV gene and allele were boxed and classified with alphabetic letters. Leader region (L-PART1â +â L-PART2), CDR-IMGT and FR-IMGT are also indicated, according to the IMGT unique numbering for V-DOMAIN [27]. The five conserved AA of the V-DOMAIN (1st-CYS 23, CONSERVED-TRP 41, hydrophobic AA 89, 2nd-CYS 104 and J-PHE 118) are indicated in bold. The AA changes between genes and allele of the same TRAV subgroup, if any, are shaded. The name of the clones is also reported. (DOC 135 kb)

Description of the TRAV/TRDV ORF and pseudogenes. (DOC 87 kb)

of Sheep (Ovis aries) T cell receptor alpha (TRA) and delta (TRD) genes and genomic organization of the TRA/TRD locus