Receptor Schema (Experimental)#

General#

The purpose of the Receptor object is to represent reactivity data of actual Receptors, i.e., Ig or TCR, either directly or indirectly. To this end, the Receptor object has two main sections:

The receptor_* properties: These properties describe the receptor as an abstract and global concept, i.e., the actual Ig/TCR protein complex MAY or MAY NOT have been observed in the current study. However, the Rearrangements encoding the respective chains MUST be present in the studies as well as the information linking them (see below). This allows data curators to provide potential reactivities of a potential receptor by referencing to its entry in an external database (e.g., IEDB).
The reactivity_measurements array: This structure contains one or more entries, describing reactivities of the receptor that have been observed in the current study.

The Receptor object explicitly requires full sequence information of the two associated variable domains. This is considered to be an acceptable restriction from an AIRR-seq perspective, where sequencing typically precedes or takes place in combination with the determination of receptor reactivity.

Identifiers#

The Receptor objects has two properties that serve as identifiers:

receptor_id is a local identifier and its uniqueness MUST NOT be assumed beyond the scope of the study the receptor was reported in. This property can be used, e.g., to represent designations for Ig/TCR used in a manuscript.
receptor_hash is the SHA256 hash of the receptors variable domain amino acid sequences, which serves as a globally unique identifier that can be independently calculated by repositories without requiring prior communication. It is calculated as follows, where base16 designates the function described in RFC4648 Section 6:
```
lower_case(
    base16(
        sha256(
            concatenate(
                upper_case(receptor_variable_domain_1_aa),
                upper_case(receptor_variable_domain_2_aa)
            )
        )
    )
)
```

Relations to other AIRR Schema objects#

The Receptor object is only directly linked to the Cell object, which then in turn contains the references to the records in the Rearrangements that encode the respective chains of the receptor. Therefore a given rearrangement cannot directly reference to a receptor, which is also not a meaningful thing to do, as the paired chain would be unclear, but is necessary to determine a receptors reactivity.

Annotation guidelines#

Reactivity information SHOULD be provided if it was either directly recorded in the current study or is indirectly available in a public database, where it can be linked. If no information about the receptor, besides the translated amino acid sequence of the associated chains is available, the respective object MAY still be created if the curator considers this information to be beneficial, e.g., if there is some evidence (surface expression, reaction to superantigens) that the receptor is functional and present on the surface. In the absence of any such data, Receptor objects SHOULD NOT be created.

Note on cells expressing more than a single receptor#

Cells that express more than a single IGH/TRB/TRD or a single IGK/IGL/TRA/TRG chain are regularly observered as allelic exclusion is never complete and its efficiency is rather low for loci like TRA. Such dual-expressing cells can technically be accommodated in the current AIRR Schema as an individual Cell object can link to more than two rearrangemts and to more than a single Receptor. In the case of two potential receptors, both MAY be created as an objects, if the general annotation rules are met (i.e., the direct or indirect presence of reactivity information) for each of them. Note that the annotation of cell-based reactivity information is currently not supported for dual-expressing cells, in this case additional information confirming the reactivity of one of the receptors would be required.

Representation of bi-specific antibodies#

The goal of the AIRR Standards is primarily to represent naturally occuring receptors. While bi-specific antibodies may arise in dual IGK/IGL expressing B cells their individual reactivity is not measured on a regular basis. Therefore they are currently not supported in the Receptor schema.

Receptor Fields#

Download as TSV

Name	Type	Attributes	Definition
`receptor_id`	string	required, identifier	ID of the current Receptor object, unique within the local repository.
`receptor_hash`	string	required	The SHA256 hash of the receptor amino acid sequence, calculated on the concatenated `receptor_variable_domain_*_aa` sequences and represented as base16-encoded string.
`receptor_type`	string	required	The top-level receptor type, either Immunoglobulin (Ig) or T Cell Receptor (TCR).
`receptor_variable_domain_1_aa`	string	required	Complete amino acid sequence of the mature variable domain of the Ig heavy, TCR beta or TCR delta chain. The mature variable domain is defined as encompassing all AA from and including first AA after the the signal peptide to and including the last AA that is completely encoded by the J gene.
`receptor_variable_domain_1_locus`	string	required	Locus from which the variable domain in receptor_variable_domain_1_aa originates
`receptor_variable_domain_2_aa`	string	required	Complete amino acid sequence of the mature variable domain of the Ig light, TCR alpha or TCR gamma chain. The mature variable domain is defined as encompassing all AA from and including first AA after the the signal peptide to and including the last AA that is completely encoded by the J gene.
`receptor_variable_domain_2_locus`	string	required	Locus from which the variable domain in receptor_variable_domain_2_aa originates
`receptor_ref`	array of string	optional, nullable	Array of receptor identifiers defined for the Receptor object
`reactivity_measurements`	array of ReceptorReactivity	optional, nullable	Records of reactivity measurement

Receptor Schema (Experimental)

Contents