Similar to getting lost in a language when moving country, you might encounter a language barrier when moving research fields. This dictionary will guide you in the complex world of immunoinformatics, with a focus on antibodies. Whether your main research will be in this field, you want to apply your machine learning model on antibodies, or you just want to understand the research performed in OPIG, this dictionary will get you started.

The Antibody Dictionary:

Affinity maturation: The optimisation process of naive antibodies to memory antibodies such that the antibody is optimised for a specific antigen. 

Antibody: (immunoglobulin) a Y-shaped molecule important in the adaptive immune system. A canonical antibody consists of two identical heavy chains and two identical smaller light chains. 

Antibody phage display: Bacteriophages can be genetically modified to present antibodies on their surface. The displayed antibodies could be used for selection and screening. 

Antigen: The molecule to which an antibody binds.

B-cells: (B lymphocytes) A type of white blood cells that produce antibodies. These antibodies can be secreted or presented on the membrane of the B-cell.   

Canonical form: Except for the CDRH3, CDR loops can be individually clustered based on structures. CDR loops in the same conformational cluster have the same canonical form. 

CDR: Complementarity-determining regions. The variable loops of the antibody that are important for antigen binding. Both the heavy and light chain contain three CDRs and thus one Fv has six CDRS (CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, CDRL3). CDRH3 is the most variable loop. 

Clonotyping: Clustering of antibodies derived from the same genes, and therefore originating from the same progenitor B-cell. 

Developability: The potency of the antibody to become a therapeutic. This term includes antibody properties such as immunogenicity, solubility, specificity, stability, manufacturability, and storability.  

Epitope: The set of residues on the antigen to which the antibody binds. 

Framework: The folded beta-sheets that make up the majority of the Fv and combines the CDR loops. 

Fv: The variable regions of the heavy and light chain. An antibody contains two Fvs.

Germline: The germline genes encode for the antibody. The heavy chain is encoded by 3 genes: V, D and J. The light chain is encoded by 2 genes: V and J. 

Humanisation: Increasing the humanness of an antibody. Animal derived antibodies need to undergo a humanisation process to reduce immunogenicity.
 
Hybridoma: The technique to obtain a large set of identical antibodies by immunizing an animal model with the antigen of interest. The collected B-cells of the animal are fused with myeloma cells to form immortal hybridoma cell lines that produce the antibody of interest. 

Immunogenicity: The ability to provoke an immune response. A therapeutic antibody should have a low immunogenicity to be functional. 

Liability: Motifs in the antibody sequence that can affect the binding ability or developability of the antibody. This includes, among others, post-translational modifications. 

Memory B-cells: B-cells that have previously been exposed to an antigen and produces antibodies optimised for this specific antigen. 

Naive B-cells: B-cells that have not been exposed to antigens. Antibodies of these cells have not been optimised for a specific antigen. 

Nanobody: An antibody variant consisting of only the variable heavy chain region. Nanobodies can naturally be found in, among others, Llamas.  

Numbering schemes: Numbering system to assign the same number to aligned antibody positions. These schemes allow for comparison of residues in similar positions in the antibody. These numbering schemes are needed as the framework and, in particular, CDR loops might vary in the number of residues. 

Paratope: The set of residues on the antibody which bind to the antigen. The paratope consists mainly of CDR residues but could also include framework regions. 

Plasmablast: Short-lived antibody secreting cells produced in an early antibody response. 

Repertoire: The collection of distinct antibodies or B-cells found in a particular individual or tissue. 

Residues: The amino acids that make up the antibody sequence. 

ScFv: The single chain variable fragment is an antibody variant consisting of a variable heavy and variable light chain connected with a flexible peptide linker. 

Single domain antibody: An antibody variant consisting of only the variable heavy chain or the variable light chain.  

Somatic hypermutation: mutations to increase the affinity of the antibody for its cognate antigen during the affinity maturation process. 

V(D)J gene recombination: The somatic recombination of the genes encoding for the antibody. Combinations of different genes allow for diverse antibodies. 

Vernier zone: Framework residues that underlie the CDR loops and are expected to be important for the structural conformation of these loops. Therefore, mutations in these regions can affect binding affinity.