A prominent natural H-2 Kd ligand is derived from protein tyrosine kinase JAK1.

The first natural MHC ligand to be sequenced directly was the nonapeptide SYFPEITHI eluted from H-2 Kd molecules of a mouse tumour line, P815 [1]. A GenBank search indicated high homology to a nonapeptide contained within the human tyrosine kinase JAK1: SFFPEITHI, residues 355-363 [2]. This high homology prompted us to look at whether the mouse JAK1 protein has a Tyr residue at position 356 instead of Phe as in the human sequence. Cloning and sequencing of the mouse homologue gene confirmed that this is indeed the case. Thus, the physiological MHC ligand SYFPEITHI is derived from the protein tyrosine kinase, JAK1. The mouse tumor line P815 expresses the 5.4-kb JAK1 mRNA, and the 130,000 kDa JAK1 protein can be readily detected.