Two types of subset-defining VH CDR3 sequence patterns. (A) Mainly combinatorial. The pattern typical of subset 8 is exclusively composed of amino acids encoded by the unmutated D region of the IGHD6-13 and 5′J region of the IGHJ5 genes, whereas the junctional N-diversity regions (N1 and N2) are diverse. (B) Combinatorial+junctional. The pattern defining subset 4 consists of the junctional N2 amino acids [KR]R at positions 112.4 (tip of the CDR3 loop) and 112.3 and of the IGHJ6-encoded motif YYYYG. The height of symbols within the stack indicates the relative frequency of each amino acid at that position. Amino acid position is according to the IMGT numbering for the V domain.²⁷