Receptor Schema#

The purpose of the Receptor object is to provide an structure for information referring to actual Receptors, i.e., Ig or TCR, both for outgoing and incoming links. To this end, the Receptor object describes the receptor as an abstract and global concept, i.e., the actual Ig/TCR protein complex, which MAY or MAY NOT have been observed in the current study. However, the rearrangements encoding the respective chains MUST be present in the study as well as the information linking them (see below). In addition the object allow references to entries in external database (e.g., IEDB).

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#

References to information describing the same receptor located in other databases (i.e., outgoing links) SHOULD be provided as as CURIEs in the receptor_ref property. Entries in this array MUST refer to objects that a conceptually similar to the Receptor concept used by the AIRR Schema. Linkage to potentially existing reactivity information needs is expected to happen in the external database, not in the Receptor record.

Receptor objects SHOULD be created even in the absence of additional external information, as this will enhance the discoverability of AIRR-seq experiments in which a receptor might have been present. This especially applies to experiments that provide further evidence (e.g., surface expression, reaction to superantigens) showing that a receptor is functional and present on the surface.

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 objects, if the general annotation rules are met for each of them. Note that the annotation of cell-based reactivity information is handled by the Cell Reactivity Schema (Experimental) object.

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

Identifier for the Receptor object. This identifier must be unique within a given study, but it is recommended that it be a universally unique record locator to enable database applications.

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